System and method for health monitoring including a user device and biosensor

ABSTRACT

A biosensor unit is coupled to a user device and may communicate with the user device over a short range wireless or wired interface. The biosensor unit includes an optical sensor used to obtain a plurality of PPG signals. The PPG signals are used to obtain an oxygen saturation level, a heart rate and a respiration rate of a user. The PPG signal may also be used to obtain a nitric oxide (NO) level and glucose level of the user. The user device may generate a graphical user interface to display the biosensor data to a user.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims priority under 35 U.S.C. § 120 as acontinuation application to U.S. patent application Ser. No. 15/404,117filed Jan. 11, 2017 entitled “SYSTEM AND METHOD FOR HEALTH MONITORINGINCLUDING A USER DEVICE AND BIOSENSOR, and is hereby expresslyincorporated by reference herein, which claims priority as acontinuation in part application to the following:

-   -   U.S. patent application Ser. No. 15/400,916 entitled, “SYSTEM        AND METHOD FOR HEALTH MONITORING INCLUDING A REMOTE DEVICE,”        filed Jan. 6, 2017, and issued as U.S. Pat. No. 10,750,981        issued Aug. 25, 2020 and hereby expressly incorporated by        reference herein;    -   U.S. patent application Ser. No. 15/276,760 entitled, “SYSTEM        AND METHOD FOR A DRUG DELIVERY AND BIOSENSOR PATCH,” filed Sep.        26, 2016 and issued as U.S. Pat. No. 9,636,457 on May 2, 2017,        and hereby expressly incorporated by reference herein;    -   U.S. patent application Ser. No. 15/275,444 entitled, “SYSTEM        AND METHOD FOR A BIOSENSOR MONITORING AND TRACKING BAND,” filed        Sep. 25, 2016, and issued as U.S. Pat. No. 9,642,538 on May 9,        2017, and hereby expressly incorporated by reference herein;    -   U.S. patent application Ser. No. 15/275,388 entitled, “SYSTEM        AND METHOD FOR HEALTH MONITORING USING A NON-INVASIVE,        MULTI-BAND BIOSENSOR 500,” filed Sep. 24, 2016 and issued as        U.S. Pat. No. 9,642,578 on May 9, 2017, and hereby expressly        incorporated by reference herein; and    -   U.S. patent application Ser. No. 14/866,500 entitled, “SYSTEM        AND METHOD FOR GLUCOSE MONITORING,” filed Sep. 25, 2015 and        issued as U.S. Pat. No. 10,321,860 on Jun. 18, 2019, and hereby        expressly incorporated by reference herein.

The present application claims priority under 35 U.S.C. § 120 as acontinuation in part application to U.S. patent application Ser. No.15/718,721 entitled, “SYSTEM AND METHOD FOR MONITORING NITRIC OXIDELEVELS USING A NON-INVASIVE, MULTI-BAND BIOSENSOR,” filed Sep. 28, 2017and issued as U.S. Pat. No. 10,517,515 on Dec. 31, 2019 and herebyexpressly incorporated by reference herein, which claims priority as acontinuation application to U.S. patent application Ser. No. 15/622,941entitled, “SYSTEM AND METHOD FOR MONITORING NITRIC OXIDE LEVELS USING ANON-INVASIVE, MULTI-BAND BIOSENSOR,” filed Jun. 14, 2017 and issued asU.S. Pat. No. 9,788,767 on Oct. 17, 2017, and hereby expresslyincorporated by reference herein.

The present application claims priority under 35 U.S.C. § 120 as acontinuation in part application to U.S. patent application Ser. No.15/680,991 entitled, “SYSTEM AND METHOD FOR DETECTING A SEPSISCONDITION,” filed Aug. 18, 2017 and issued as U.S. Pat. No. 9,968,289 onMay 15, 2018, and hereby expressly incorporated by reference herein.

The present application claims priority under 35 U.S.C. § 120 as acontinuation in part application to U.S. patent application Ser. No.15/462,700 entitled, “SYSTEM AND METHOD FOR ATOMIZING AND MONITORING ADRUG CARTRIDGE DURING INHALATION TREATMENTS,” filed Mar. 17, 2017 andissued as U.S. Pat. No. 10,500,354 on Dec. 10, 2019 and hereby expresslyincorporated by reference herein, which claims priority under 35 U.S.C.§ 119(e) to U.S. Provisional Application No. 62/457,138 entitled,“SYSTEM AND METHOD FOR ATOMIZING AND MONITORING A DRUG CARTRIDGE DURINGINHALATION TREATMENTS,” filed Feb. 9, 2017 and hereby expresslyincorporated by reference herein.

FIELD

This application relates to systems and methods of non-invasive,autonomous health monitoring and drug administration using a biosensorand user device.

BACKGROUND

Various techniques are available for obtaining biosensor measurements,such as blood glucose levels in patients with diabetes. One techniquerequires a small blood sample from the patients, e.g. from a fingerprick. The blood sample is placed on a chemically prepared test stripand inserted into a glucose meter that analyzes the test strip andprovides a blood glucose level. Unfortunately, to monitor their bloodglucose levels, diabetics may need to prick their fingers multiple timeswithin a day. This monitoring process can be painful, inconvenient andcreates possible exposure to infections. Additionally, measurements withthese devices present an error of uncertainty range betweenapproximately 10-20% depending on sample quality, human error,calibration, humidity, and hygiene in the sample area. Thus, there is aneed for an accurate, non-invasive blood analytic and glucose monitoringand tracking system and method and device that eliminates the pain ofdrawing blood as well as eliminates a source of potential infection.

In addition, there is a need for accurate and non-invasive biosensormeasurements, such as pulse, blood oxygen level, electrolyte levels,etc. It is important to provide a convenient system for monitoring andtracking these biosensor measurements.

In addition, there is a need for a more accurate and non-invasive drugadministration device based on biosensor monitoring and feedback.

SUMMARY

According to a first aspect, user equipment includes a display and atleast one transceiver configured to communicate with an externalbiosensor, wherein the at least one transceiver receives biosensor datafrom the biosensor. The user equipment further includes at least oneprocessing circuit and at least one memory device, wherein the at leastone memory device stores instructions which when executed by the atleast one processing device, causes the user equipment to process thebiosensor data to determine a level of nitric oxide (NO) in blood flow,wherein the biosensor data includes a first PPG signal at a firstwavelength and a second PPG signal at a second wavelength and generate agraphical user interface (GUI) that displays the biosensor data on thedisplay of the user equipment.

According to a second aspect, user equipment includes a display and atleast one transceiver configured to communicate over a cellular networkand to an external biosensor. The user equipment further includes atleast one processing circuit and at least one memory device, wherein theat least one memory device stores instructions which when executed bythe at least one processing device, causes the user equipment to obtaina value L_(λ1) using an AC component of a first PPG signal; obtain avalue L_(λ2) using an AC component of a second PPG signal; obtain avalue R_(λ1, λ2) from a ratio including the value L_(λ1) and the valueL_(λ2); obtain a blood glucose level using the value R_(λ1, λ2); andgenerate a graphical user interface that includes the blood glucoselevel on the display.

According to a third aspect, user equipment includes one or moretransceivers configured to communicate over a cellular network and to atleast one external biosensor. The user equipment also includes at leastone processing circuit and at least one memory device, wherein the atleast one memory device stores instructions which when executed by theat least one processing device, causes the user equipment to obtain afirst AC component of a first PPG signal around a first wavelength oflight (λ1), wherein the first wavelength of light is in a range of 370nm to 410 nm; obtain a second AC component of a second PPG signal arounda second wavelength of light (λ1), wherein the second wavelength oflight is in an infrared (IR) range; and obtain an R value from a ratioincluding the first AC component and the second AC component.

In one or more of the above aspects, the user equipment is furtherconfigured to generate a GUI that displays one or more commands forcontrolling the biosensor; receive user input indicating a command forthe biosensor; and transmit a command to the biosensor in response tothe user input.

In one or more of the above aspects, the first wavelength of light has ahigh absorption coefficient for nitric oxide (NO) levels in blood flowand the second wavelength of light has a low absorption coefficient forNO levels in blood flow.

In one or more of the above aspects, the user equipment is configured toobtain a value L_(λ1) using a first PPG signal; obtain a value L_(λ2)using the second PPG signal; and determine a value R_(λ1, λ2) using aratio including the value L_(λ1) and the value L_(λ2). The userequipment is configured to determine a level of nitric oxide (NO) inblood flow using at least the value R_(λ1, λ2).

In one or more of the above aspects, the user equipment is configured toobtain a blood glucose concentration level using at least the valueR_(λ1, λ2) and a calibration.

In one or more of the above aspects, the user equipment is configured todetermine a level of vasodilation using the biosensor data, wherein thelevel of vasodilation includes a measurement of a localized change inwidth of a vessel from a localized relaxation of vascular muscle cellswithin the vessel walls.

In one or more of the above aspects, the biosensor is implemented in afinger attachment and the user equipment includes a smart phone.

In one or more of the above aspects, the user equipment is configured togenerate a command to a drug administrative device to administermedication.

In one or more of the above aspects, the user equipment is configured togenerate a message with the blood glucose level to a third party healthcare provider and transmit the message over a wide area network to thethird party health care provider.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an exemplary embodiment of user equipment (UE) forhealth monitoring.

FIG. 2 illustrates a schematic block diagram of an embodiment of theuser equipment in more detail.

FIG. 3 illustrates a schematic block diagram of an exemplary embodimentof a biosensor.

FIG. 4 illustrates an exemplary embodiment of a drug administrativedevice.

FIG. 5A illustrates a logical flow diagram of an embodiment of a methodfor administration of medication using the UE.

FIG. 5B illustrates a logical flow diagram of an embodiment of anothermethod for administration of medication using the UE.

FIG. 6 illustrates an embodiment of a wearable shirt button with anintegrated button biosensor.

FIG. 7 illustrates a schematic block diagram of an exemplary embodimentof another form factor of the biosensor.

FIG. 8A illustrates an exemplary embodiment of another form factor ofthe biosensor.

FIG. 8B illustrates an exemplary embodiment of another form factor ofthe biosensor.

FIG. 9 illustrates an embodiment of a graphical user interface (GUI)displayed on the UE.

FIG. 10 illustrates an embodiment of a graphical user interface (GUI)900 displayed on another embodiment of the UE.

FIG. 11 illustrates a schematic block diagram of an embodiment of agraphical user interface (GUI) generated by the health monitoringapplication.

FIG. 12 illustrates a schematic block diagram of an embodiment of agraphical user interface (GUI) generated by the health monitoringapplication.

FIG. 13 illustrates a schematic block diagram of an embodiment of agraphical user interface (GUI) generated by the health monitoringapplication.

FIG. 14A illustrates a logical flow diagram of an embodiment of a methodof operation of the health monitoring application of the UE.

FIG. 14B illustrates a logical flow diagram of an embodiment of anothermethod of operation of the health monitoring application of the UE.

FIG. 15 illustrates a schematic block diagram of an embodiment of anexemplary communication network in which the devices described hereinmay operate.

FIG. 16 illustrates a logic flow diagram of an embodiment of anothermethod of operation of the health monitoring application of the UE.

FIG. 17 illustrates a schematic block diagram illustrating an embodimentof the PPG circuit in more detail.

FIG. 18 illustrates a schematic block diagram of another exemplaryembodiment of the the PPG circuit.

FIG. 19 illustrates a schematic block diagram of an embodiment of thePPG circuit with a plurality of photodetectors.

FIG. 20 illustrates a schematic diagram of a graph of actual clinicaldata obtained using PPG techniques at a plurality of wavelengths.

FIG. 21 illustrates a logical flow diagram of an embodiment of a methodof the biosensor.

FIG. 22 illustrates a logical flow diagram of an embodiment of a methodof determining concentration levels of one or more substances in moredetail.

FIG. 23A illustrates a graph of an embodiment of an output of a broadspectrum light source.

FIG. 23B illustrates a graph with an embodiment of an exemplary spectralresponse of detected light across a broad spectrum.

FIG. 24 illustrates a schematic block diagram of an embodiment of amethod for determining concentration levels or indicators of substancesin pulsating blood flow in more detail.

FIG. 25 illustrates a logical flow diagram of an exemplary method todetermine an absorption coefficients of a substance at a wavelength λ.

FIG. 26 illustrates a schematic drawing of another exemplary embodimentof results of clinical data obtained using an embodiment of thebiosensor from a second patient.

FIG. 27 illustrates a schematic drawing of another exemplary embodimentof results of clinical data obtained using an embodiment of thebiosensor from a third patient.

FIG. 28 illustrates a schematic drawing of another exemplary embodimentof results of clinical data obtained using the biosensor from a fourthpatient.

FIG. 29 illustrates an exemplary graph of spectral responses of aplurality of wavelengths from clinical data using the biosensor.

FIG. 30 illustrates an exemplary graph of spectral responses of aplurality of wavelengths from clinical data using the biosensor.

FIG. 31 illustrates an exemplary graph of spectral responses of aplurality of wavelengths from clinical data using the biosensor.

DETAILED DESCRIPTION

The word “exemplary” or “embodiment” is used herein to mean “serving asan example, instance, or illustration.” Any implementation or aspectdescribed herein as “exemplary” or as an “embodiment” is not necessarilyto be construed as preferred or advantageous over other aspects of thedisclosure. Likewise, the term “aspects” does not require that allaspects of the disclosure include the discussed feature, advantage, ormode of operation.

Embodiments will now be described in detail with reference to theaccompanying drawings. In the following description, numerous specificdetails are set forth in order to provide a thorough understanding ofthe aspects described herein. It will be apparent, however, to oneskilled in the art, that these and other aspects may be practicedwithout some or all of these specific details. In addition, well knownsteps in a method of a process may be omitted from flow diagramspresented herein in order not to obscure the aspects of the disclosure.Similarly, well known components in a device may be omitted from figuresand descriptions thereof presented herein in order not to obscure theaspects of the disclosure.

Overview

User equipment (UE) includes a smart phone, tablet, watch, laptop, orother type of portable user device. The UE is configured to collectbiosensor data from one or more integrated biosensors or by receivingbiosensor data from one or more external biosensors through a wirelessor a wired connection. The UE includes a Health Monitoring (HM)application. The HM application is configured to receive the biosensordata and display the biosensor data on the display of the UE. The UE mayalso communicate biosensor data over a local or wide area network to athird party, such as a pharmacy or physician's office.

In an embodiment, the integrated or external biosensors may include apulse oximeter configured to detect pulse and blood oxygen levels. Theintegrated or external biosensors may also include a temperature sensorto detect body temperature. In an embodiment, at least one of theintegrated or external biosensors includes a PPG circuit configured todetect one or more substances in blood, such as an indicator of glucoselevels in arterial blood flow or blood levels of other substances, suchas bilirubin, sodium, potassium, or even blood alcohol levels.

Embodiment—User Equipment for Health Monitoring

FIG. 1 illustrates an exemplary embodiment of user equipment (UE) 100for health monitoring. The UE 100 may include a smart phone, tablet,watch, laptop, or other type of portable user device. The UE 100includes a processing circuit 102 and a memory device 104 that storesinstructions that when performed by the processing circuit 102 mayperform one or more of the functions described herein with respect tothe UE 100. The UE 100 includes a biosensor interface 106 that isconfigured to collect biosensor data from an integrated biosensor 150Aand/or by receiving biosensor data from one or more external biosensors150B, 150C through a wireless or a wired connection.

The UE 100 may also include a wireless and/or wired transceiver 110 anddisplay 112. In one aspect, the UE 100 further includes a HealthMonitoring (HM) application 108 stored in the memory device 104. Theprocessing circuit 102 is configured to process one or more instructionsof the HM application 108 to perform one or more of the functionsdescribed herein. The HM application 108 processes biosensor data anddisplays the biosensor data on the display 112. The HM application 108may also generate messages for transmission to third parties by thetransceiver 110.

For example, the HM application 108 may generate messages that includerequests to refill medications that are transmitted to a pharmacy over awide area network (WAN) using the transceiver 110. In another example,the HM application 108 may generate messages that include patient healthdata that are transmitted to a doctor's hospital.

FIG. 2 illustrates a schematic block diagram of an embodiment of theuser equipment 100 in more detail. The components of the UE 100described herein are exemplary and additional or alternative componentsand functions may be implemented. In addition, one or more of thefunctions or components shown herein may not be present or may becombined with other components or functions. The UE 100 includes thedisplay 112, the processing circuit 102 and the memory device 104. Thememory device 104 may include a managed object 202 that stores the HMapplication 108 for instructing the UE 100 to perform one or more of thefunctions described herein.

The UE 100 further includes a transceiver 110. The transceiver 110 mayinclude one or more of a Bluetooth transceiver 204, a WLAN (IEEE 802.11xcompliant) transceiver 206, and a global positioning satellite (GPS)transceiver 210. The WLAN transceiver 206 may operate as a non-3GPPaccess interface to a WLAN network, e.g. compliant with one or morestandards under IEEE 802.11 protocols. The UE 100 also includes a mobileradio frequency (RF) transceiver 208 configured to communicate over acellular network. For example, the mobile RF transceiver 208 maycommunicate voice calls over cellular networks that are, e.g., compliantwith Universal Mobile Telecommunications System (UMTS) Terrestrial RadioAccess Network (UTRAN), Long Term Evolution (LTE) Evolved UTRAN(E-UTRAN), LTE-Advanced (LTE-A) and/or other wireless cellular network.The UE 100 may also include one or more wireline transceivers, such as auniversal serial bus (USB) transceiver 212 or Ethernet/IP transceiver214. In other embodiments, the transceiver 110 may operate in one ormore other wireless frequency bands or protocols, such as near fieldcommunication, short range radio frequency, RFID, or other wirelesscommunication protocol.

The UE 100 may further include an AC adapter 216, battery module 218 anda power management unit 220. The power management unit 220 helps tocontrol power functions of the UE 100. When the UE 100 includes acellular phone, the UE 100 may include a Universal Subscriber IdentityModule (USIM) application 224 on an a smart card such as a UniversalIntegrated Circuit Card (UICC) 226. The UE 100 may further include oneor more user devices, such a digital camera 230, touch screen controller232, speaker 234 and microphone 236. The UE 100 may include one or moreadditional user interfaces 240, such as a keypad, touch screen, touchpad, etc. For example, the UE 100 may include a mouse and use an IR orvisible light to move a pointer or other icon on the display 112 toselect commands to control one or more biosensors and/or and the HMapplication 108. The user interface 240 may include a touch pad toselect commands on the display 112 that controls operation of the UE 100and/or HM application 108. In another embodiment, the UE 100 includes atouch screen that displays graphical user interfaces having selectionsand commands for controlling the UE 100 or HM application 108. One ormore internal communication buses (not shown) communicatively couple thecomponents of the UE 100.

In an embodiment, the UE 100 is configured to collect biosensor data,e.g. either by receiving biosensor data from external biosensors 150through the biosensor interface 106 or from one or more integratedbiosensors 150. For example, the biosensor 150 may include one or moresensors, such as a temperature sensor (contact or non-contact), a pulseoximeter circuit, a blood pressure circuit, or a PPG circuit, asdescribed in more detail herein. In addition, the UE 100 may communicatewith external biosensors 150 using the transceiver 110 to receivebiosensor data.

The UE 100 may also include an activity monitoring circuit 260. Inanother embodiment, the UE 100 communicates with an external activitymonitoring device, such as a FitBit® wireless wristband or otherexternal activity tracker. The HM application 108 may collect activityinformation, such as periods of rest, periods of activity, steps walkedor run, etc. The HM application 108 may then instruct the UE 100 todisplay a graphical user interface (GUI) illustrating the activityinformation for one or more users.

The UE 100 may also include an integrated Drug Administration Device 250and/or a Drug Administration Device Interface 262 that is configured todeliver medication to a patient in response to the biosensor data. Forexample, the Drug Administration Device 250 may include an external orintegrated skin patch, IV drug pump, etc.

In an embodiment, the health monitoring (HM) application 108 processesthe biosensor data, such as measurements made by the biosensors, andgenerates health monitoring data. For example, the HM application mayinstruct the processing circuit 102 to execute logic to processbiosensor data to determine blood pressure, pulse rate, blood oxygensaturation levels (SpO₂), electrocardiogram (EKG or ECG), etc. The HMapplication may generate one or more graphical user interfaces (GUI).The GUIs present the biosensor data received or processed by the UE 100as well as user commands to control the biosensors. The UE 100 may alsocommunicate biosensor data with other user equipment.

FIG. 3 illustrates a schematic block diagram of an exemplary embodimentof a biosensor 150. The biosensor 150 may be integrated with the UE 100or may be external to the UE 100 and wirelessly communicate with the UE100. When located externally, the biosensor 150 may include a separateprocessing circuit 302, memory device 304, transceiver 310 and battery312. When integrated with the UE 100, the biosensor 150 may include oneor more of these separate components or utilize the processing circuit102, memory device 104, battery module 218, transceiver 110 or othercomponents of the UE 100.

The processing circuit 302 is communicatively coupled to the memorydevice 304. In one aspect, the memory device 304 may include one or morenon-transitory processor readable memories that store instructions whichwhen executed by the processing circuit 302, causes the processingcircuit 302 to perform one or more functions described herein. Thememory device 304 may also include an EEPROM to store one or morepatient identifications (ID) 306, wherein each of the patient IDs 306are associated with a user being monitored by the biosensor 150. Thememory device 304 may also store an electronic medical record (EMR) 308or portion of an EMR 308 associated with each of the patient IDs 306.The biosensor 150 may thus be used to monitor multiple users or patientsassociated with different patient IDs 306. The biosensor data obtainedby the biosensor 150 may be stored in the EMR 308 associated with thepatient ID 306 of the monitored user. The processing circuit 302 may beco-located with one or more of the other circuits in the biosensor 150in a same physical encasement or located separately in a differentphysical encasement or located remotely.

The biosensor 150 may further include a transceiver 310, for example,when the biosensor 150 is external to the UE 100. The transceiver 710may transmit the patient ID 306 and associated biosensor data to the UE100. The transceiver 310 may include a wireless or wired transceiverconfigured to communicate with the UE 100 over a USB port or short rangewireless interface or over a LAN, MAN and/or WAN. In one aspect, thetransceiver 310 may include IEEE 802.11ah, Zigbee, IEEE 802.15-11 orWLAN (such as an IEEE 802.11 standard protocol) compliant transceiver,RFID, short range radio frequency, Bluetooth, infrared link, or otherwireless communication protocol. In another aspect, the transceiver 310may also include or alternatively include an interface for communicatingover a cellular network. In an embodiment, the transceiver 310 mayinclude a thin foil for an antenna that is specially cut and includes acarbon pad contact to a main PCB of the biosensor 150. This type ofantenna is inexpensive to manufacture and may be printed on the insideof an enclosure for the biosensor 150 situated away from the skin of thepatient to minimize absorption. The transceiver 310 may also include awired transceiver interface, e.g., a USB port or other type of wiredconnection, for communication with the UE 100 or one or more otherdevices over a LAN, MAN and/or WAN. In an embodiment, the biosensor 150is battery operated and includes a battery 312, such as a lithium ionbattery.

The biosensor 150 includes one or more types of sensors, such asphotoplethysmography (PPG) circuit 300, a temperature sensor 320, pulseoximeter circuit 322 or blood pressure circuit 324. The temperaturesensor 320 is configured to detect a temperature of a patient. Forexample, the temperature sensor 320 may include an array of sensors(e.g., 16×16 pixels) positioned on a side of the biosensor 150. Thearray of sensors then detects an indication of the temperature of thepatient from the skin. In another embodiment, the biosensor 150 mayinclude a thermopile infrared (IR) temperature sensor. In use, a userswipes the biosensor 150 over their forehead or other area of the body.The biosensor 150 detects the temperature and transmits the temperatureto the HM application 108 for storage and tracking. The HM application108 may instruct the UE 100 to display a graphical user interface (GUI)illustrating a current temperature and a history of temperature readingsfor the user.

The pulse oximeter circuit 322 detects pulse or heart rate and bloodoxygen saturation levels (SpO₂) and transmits the biosensor data to theHM application 108 for storage and tracking. The HM application 108 mayinstruct the UE 100 to display a graphical user interface (GUI)illustrating a current pulse and blood oxygen level and a history ofheart rate and blood oxygen levels for one or more users. In addition,the pulse oximeter circuit 322 may be configured to monitor blood flow.For example, the biosensor 150 monitors and transmits heart ratemeasurements from one or more extremities, such as the arms and legs ofthe user, as well as from a chest/heart area of the user. The user maymove the biosensor 150 to the plurality of positions or multiplebiosensors 150 may be used. The heart rate readings from the heart/chestarea and from the one or more extremities of the user are monitored andtracked by the HM application 108 of the UE 100. The heart rate readingsare used to determine and track blood flow between the heart and the oneor more extremities. Based on the heart rate readings, the HMapplication 108 may determine potential blockages in blood flow.

The blood pressure sensor 324 detects blood pressure and transmits theblood pressure to the HM application 108 for storage and tracking. TheHM application 108 may instruct the UE 100 to display a graphical userinterface (GUI) illustrating a current blood pressure and a history ofblood pressure readings for one or more users.

In an embodiment, the UE 100 may include a photoplethysmography (PPG)circuit 300. The PPG circuit 300 is configured to generate at least afirst spectral response for light reflected around a first wavelengthfrom skin tissue of the patient, generate at least a second spectralresponse for light detected around a second wavelength reflected fromthe skin tissue of the patient. The processing circuit 302 is configuredto process the first and second spectral responses at the firstwavelength and the second wavelength and determine biosensor data usingthe first and second spectral responses. For example, the biosensor datamay include oxygen saturation levels and pulse rate. The PPG circuit 300may thus be included as the pulse oximeter circuit 322 or in addition toa separate pulse oximeter circuit 322. In addition, the PPG circuit 300may also obtain concentration levels of one or more substances inarterial blood flow using first and second spectral responses atpredetermined wavelengths. For example, the PPG circuit 300 maydetermine an indicator of glucose levels, analyte levels, blood alcohollevels, etc. The operation of the PPG circuit 300 is described in moredetail herein.

The activity monitoring circuit 260 is configured to monitor theactivity level of a user or patient of the biosensor 150. For example,the activity monitoring circuit 260 may include a multiple axesaccelerometer that measures a position of the patient and motion of thepatient. In one aspect, the activity monitoring circuit 260 determinesperiods of activity and rest. For example, the activity monitoringcircuit 260 monitors and records periods of rest that meet apredetermined threshold of low motion or activity level, such assitting, lying, sleeping, etc. The activity monitoring circuit 260 mayalso monitor and record periods of activity that meet a predeterminedthreshold of motion or activity level, such as walking, running,lifting, squatting, etc. The biosensor 150 is then configured to measureand store biosensor data, such as the patient vitals, with an indicatorof the activity level of the patient. For example, blood oxygen levelsmay vary greatly in patients with COPD during rest and activity.Biosensor data, such as the vitals of the patient, are tracked duringperiods of activity and rest and the level of activity at time ofmeasuring the vitals is recorded. The biosensor 150 is thus configuredto associate measurements of patient vitals, such as pulse rate, bloodoxygen levels, temperature, etc., with the activity level of thepatient. The biosensor 150 may also track levels of substances in theblood using the PPG circuit 300 and the associated level of activity ofthe patient. For example, the biosensor 150 may track an indicator ofglucose levels in the blood and the activity level of a user over a day,week, month, etc.

In another aspect, to help lower power consumption, in an embodiment,the biosensor 150 includes a rest mode. For example, the activitymonitoring circuit 260 may signal a rest mode when a patient is asleepor meets a predetermined threshold of low activity level for apredetermined time period. In the rest mode, the biosensor 150 signalsone or more modules to halt non-essential processing functions. When theactivity monitoring circuit 260 detects a higher activity levelexceeding another predetermined threshold for a predetermined timeperiod, the biosensor 150 signals one or more modules to exit rest modeand resume normal functions. This activity monitoring feature helps tosave power and extend battery life of the biosensor 150.

In another aspect, the activity monitoring circuit 260 is configured toinclude a fitness tracker application. The activity monitoring circuit260 may monitor a number of steps of the patient, amount and length ofperiods of sleep, amount and length of periods of rest, amount andlength of periods of activity, etc.

The biosensor 150 may also include an integrated drug administrationdevice 250 or be communicatively coupled to a drug administration device250. The biosensor 150 may be configured to control delivery ofmedication to a patient based on biosensor data obtained by thebiosensor 150 as described in more detail in U.S. patent applicationSer. No. 15/276,760 entitled, “SYSTEM AND METHOD FOR A DRUG DELIVERY ANDBIOSENSOR PATCH,” filed Sep. 26, 2016 and hereby expressly incorporatedby reference herein.

The biosensor 150 may include a display 326. The HM application 108 isconfigured to display a graphical user interface (GUI) on the display326 that includes biosensor data and controls for the biosensor 150.

Embodiment—Drug Administrative Device

FIG. 4 illustrates an exemplary embodiment of a drug administrativedevice 400. The drug administrative device 400 includes a skin patch 402and drug pump or syringe 408. The skin patch 402 includes a wired orwireless transceiver 310 configured to communicate with the UE 100.Though the wireless transceiver 310 is illustrated as integrated withinthe skin patch 402, it may be included in one or more other parts of thedrug administrative device 400. A battery, such as a hydrogen fuel cell,may be integrated to power the wireless transceiver 310 and othercomponents of the drug administrative device 250.

The skin patch 402 may also include one or more biosensors, e.g., a PPGcircuit 300 as well as a temperature sensor 320, pulse oximeter circuit322 or blood pressure circuit 324. The pulse oximeter circuit 322 isconfigured to detect a heart rate of a patient during drug delivery.

The skin patch 402 may also include a vein detection device 414 thatassists a user, such as a patient or care giver, to locate veins orarteries. The vein detection device 414 is configured to scan adesignated area of skin using an infrared (IR) signal to locate a highIR signature that indicates the presence of a vein or an artery.Alternatively or additionally, an ultraviolet (UV) signal may be used aswell to detect the location of vein or artery. The vein detection device414 may include a sensor filter 416 that filters out ambient light andlight not reflected from the skin but passes IR light reflected from thedesignated area of the skin.

The PPG circuit 300 is configured to obtain at least a first spectralresponse for light reflected around a first wavelength from skin tissueof the patient, obtain at least a second spectral response for lightdetected around a second wavelength reflected from the skin tissue ofthe patient. A processing circuit (not shown) within the skin patch 402or PPG circuit 300 is configured to process the first and secondspectral responses at the first wavelength and the second wavelength anddetermine patient vitals using the first and second spectral responses.For example, the PPG sensor may be configured to detect oxygensaturation (SpO₂) levels in blood flow, as well as heart rate and bloodpressure.

The PPG circuit 300 may thus be included as the pulse oximeter circuit322 or blood pressure circuit 324 or in addition to a separate pulseoximeter circuit 322 or blood pressure circuit 324. In addition, the PPGcircuit 300 may also obtain concentration levels of one or moresubstances in arterial blood flow using first and second spectralresponses at predetermined wavelengths, such as an indicator of glucoselevels, analyte levels, blood alcohol levels, etc. The operation of thePPG circuit 300 is described in more detail herein.

The skin biosensor 150 may include additional or alternative components,such as an activity monitoring circuit 260, display 326, etc.

In an embodiment, the skin patch 402 is configured to administermedication to a user through the drug delivery structure 422. The drugdelivery structure 422 may include permeable material or an array ofmicroneedles. The drug delivery structure 422 may also include a drugfluid bowl that holds a predetermined dosage of the medication.

The skin patch 402 may also include an ultrasonic unit 420 that includesan ultrasonic transducer and one or more ultrasonic horns (also known asacoustic horn, sonotrode, acoustic waveguide, and ultrasonic probe)embedded in the skin patch. The ultrasonic horn is a tapering metal barcommonly used for augmenting the oscillation displacement amplitudeprovided by the ultrasonic transducer. The skin patch 402 then initiatestransdermal application of medication through a permeable material ormicroneedles while ultra-sonically transmitting energy into theepidermal layer of the skin using the ultrasonic unit 420. This processexcites pours on the sub-cutaneous layer of the skin to allow rapidabsorption of the medication.

The drug delivery structure 422 may be coupled to a syringe 408 by IVtubing 410. For example, the syringe 408 may be preloaded with themedication for administration by the skin patch 402. The UE 100 or skinpatch 402 is then configured to control the syringe to secrete apredetermined dosage of medication at a predetermined rate ofadministration. The UE 100 or skin patch 402 may also control thepredetermined dosage of medication, the predetermined rate ofadministration and period of time between dosages based on the biosensordata from the skin patch 402 or other biosensors 150. For example, theUE 100 receives real time, continuous feedback of biosensor data fromone or more biosensors 150 during periods of administration of themedication. If the UE 100 detects an allergic reaction or unsafe heartrate based on the biosensor data, the UE 100 may control the syringe 408and/or skin patch 402 to halt secretion of the medication.

In another embodiment, the UE 100 may be implemented to control a SmartInjectable Pen, a Continuous Glucose Monitoring Device and Insulin Pump,or other drug administering device. For example, the UE 100 may controlan IV infusion pump using biosensor data received from one or morebiosensors 150, such as the skin patch 402.

The syringe 408 may be powered by a battery, such as a hydrogen fuelcell 430. The hydrogen fuel cell 430 powers the syringe 408 to push thepre-loaded medications in the syringe 408 to the skin patch 402. Thesyringe 408 may include a remote control unit 432 including a processingcircuit that controls the syringe 408 to dispense a predetermined dosageof medication at a predetermined rate of administration. In anotherembodiment, the remote control unit 432 may be configured to provide fordirect injection of medication into an IV tube or catheter or a smartpen or custom IV syringe. The UE 100 communicates with the remotecontrol unit 432 to control the dosage and administration rate of themedication using continuous and real time feedback of biosensor data,such as heart rate.

FIG. 5A illustrates a logical flow diagram of an embodiment of a method500 for administration of medication using the UE 100. The HMapplication 108 generates a GUI that includes biosensor data from one ormore integrated or external biosensors 150 at 502 and displays the GUIon the UE 100. The HM application 108 may also generate and display aGUI including one or more commands for controlling a drug administrationdevice 250 at 504. The UE 100 receives user input to activate the drugadministration device 250 at 506. The user input may specify or select atype of medication, a predetermined dosage of medication, a time ofadministration or rate of administration of the medication. Based on theuser input, the HM application 108 activates the drug administrationdevice at 508.

FIG. 5B illustrates a logical flow diagram of an embodiment of a method520 for administration of medication using the UE 100. The HMapplication 108 in the UE 100 may non-invasively and continuouslymonitor a concentration of relevant substances in arterial blood flowusing one or more integrated or external biosensors 522. For example,the PPG circuit 300 using PPG techniques described herein, detects aspectral response of reflected light at one or more wavelengths. Basedon the spectral response, concentration levels of one or more relevantsubstances in surrounding tissues and/or arterial blood flow may bedetermined. For example, an indicator of insulin levels after caloricintake in arterial blood flow may be determined and monitored or a levelof white blood cells may be monitored in the arterial blood flow by thePPG circuit 300.

The UE 100 may also monitor patient vitals, such as respiratory rate,temperature, heart rate, blood pressure, blood oxygen SpO₂ levels, ECG,etc., using one or more integrated or external biosensors 150. The UE100 may also monitor other biosensor data, such as activity level, ofthe patient at 524.

The UE 100 may detect a predetermined threshold in one or moremeasurements of the patient vitals or other biosensor data at 526. Basedon the biosensor data, the UE 100 may determine to administer a dosageof medication using the drug administration device 250 at 528. Forexample, the UE 100 may detect a predetermined threshold in one or moremeasurements of the biosensor data. The UE 100 may then determine adosage amount, rate of administration and/or frequency of dosages ofmedication. The UE 100 then automatically activates a drugadministration device to administer the medication at 530 without userinput.

For example, the UE 100 may determine insulin levels after caloricintake in arterial blood flow have fallen to a predetermined threshold.The UE 100 may then determine to administer insulin to the patientthrough the drug delivery system. Based on the insulin level, the UE 100may determine a dosage amount, rate of dosage and frequency of dosages.

In another example, many people have dangerous allergic reactionsrequiring immediate attention, e.g. food allergy or insect bite allergy.The UE 100 may detect patient vitals indicating an allergic reaction anddetermine to administer a dosage of epinephrine. For example, the UE 100may detect one or more of blood pressure, respiratory rate or heart ratethat exceed a predetermined threshold indicating an allergic reaction.The UE 100 then administers epinephrine or other allergy medication inresponse to the biosensor data. The UE 100 may thus replace epi-pens inpatients with life threatening allergic reactions. Epi-pens may not beavailable or may be difficult for a person having an allergic reactionto administer. The UE 100 would automate this administration of lifesaving medication.

In an embodiment, the biosensor data is provided to a caretaker, such asa physician or pharmacy, by the UE 100. The caretaker may then instructthe UE 100 to administer the medication based on the biosensor datathrough the user interface. For example, the UE 100 may transmit analert to a physician or nurse when a patient exhibits symptoms of anallergic reaction or other condition. The UE 100 may transmit thebiosensor data with the alert. The caretaker may then instruct the UE100 to administer medication based on the biosensor data.

Embodiment—Biosensor Form Factors

Due to its compact form factor, the biosensor 150 may be configured invarious form factors, such as a skin patch, ear piece, on a button, etc.The biosensor may be configured for measurement of biosensor data onvarious skin surfaces of a patient, including on a forehead, arm, wrist,abdominal area, chest, leg, ear lobe, finger, toe, ear canal, etc.

FIG. 6 illustrates an embodiment of a wearable shirt button 600 with anintegrated button biosensor 602. The button biosensor 602 includes forexample a PPG circuit 300, an activity monitoring circuit 260, ortemperature sensor 320. The button biosensor 602, e.g., is configured tointegrate into a shirt button or clothing for measuring biosensor data.The transceiver 110 includes a wireless transceiver (positioned on anopposite side of the body facing sensor side) for communicating with theUE 100. In use, in an embodiment, the button sensor 602 detectsbiosensor data and transmits the biosensor data to the HM application inthe UE 100 for storage and tracking. The HM application may instruct theUE 100 to display a graphical user interface (GUI) illustrating thebiosensor data and a history of the biosensor data.

FIG. 7 illustrates an exemplary embodiment of another form factor of abiosensor 150. In this embodiment, a biosensor 150 is configured in anearpiece 700. The earpiece 700 includes an earbud 702. The biosensor 150is configured to transmit light into the ear canal from one or moreoptical fibers in the earbud 702 and detect light from the ear canalusing one or more optical fibers. The biosensor 150 may be powered by abattery 704. The biosensor 150 includes a wireless transceiver totransmit biosensor data to the UE 100.

FIG. 8A illustrates an exemplary embodiment of another form factor ofthe biosensor 150. In this embodiment, the biosensor 150 is configuredto attach to a finger or fingertip using finger attachment 802. Thefinger attachment 802 is configured to securely hold a finger that isinserted into the finger attachment 802. A display 800 is implemented onthe biosensor 150 with a graphical user interface (GUI) that displaysbiosensor data. For example, in use, the biosensor 150 measures bloodglucose levels using the PPG circuit 300. The blood glucose levels arethen displayed using the GUI on the display 800. The PPG circuit mayalso measure other patient vitals that are displayed on the display 800,such as oxygen saturation levels, temperature, respiration rates, heartrate, blood alcohol levels, digestive response, caloric intake, whiteblood cell count, electrolyte or other blood analyte concentrations,liver enzymes, etc. The biosensor 150 may thus provide biosensor datacontinuously and non-invasively. The finger biosensor 150 may alsoinclude a transceiver 110 to transmit biosensor data to the UE 100 fortracking and storage by the HM application 108.

FIG. 8B illustrates an exemplary embodiment of another form factor ofthe biosensor 150. In this embodiment, the biosensor 150 is configuredto attach to a finger or fingertip using finger attachment 806. Thefinger attachment 806 includes the PPG circuit 300 and is configured tosecurely hold a finger that is inserted into the finger attachment 806.The finger attachment 806 may be implemented within the same encasementas the other components of the biosensor 150 or be communicativelycoupled either through a wired or wireless interface to the othercomponents of the biosensor 150. A display 808 is implemented for thebiosensor 150 with a graphical user interface (GUI) that displaysbiosensor data including blood glucose levels. The finger biosensor 150may also include a transceiver 110 to transmit biosensor data to the UE100 for tracking and storage by the HM application 108.

The biosensor 150 may be configured to be implemented within the UE 100.In addition, one or more biosensors 150 in one or more form factors maybe used in combination with the UE 100 to determine biosensor data atone or more areas of the body. The UE 100 may then store biosensor datameasured by the one or more biosensors 150 in the EMR 708 of thepatient. The HM application 108 of the UE 100 may then utilize thebiosensor data for tracking and display or other functions.

Embodiment—HM Application

FIG. 9 illustrates an embodiment of a graphical user interface (GUI) 900displayed on the UE 100. In this example, the UE 100 includes a smartphone with a touch screen. Using the HM application 108, the UE 100 isconfigured to generate a GUI 900 for display on the display 112. Anauthorized user is operable to track biosensor data using the HMapplication 108 and control certain functions of one or more integratedor external biosensors 150 or drug administrative devices 250.

FIG. 10 illustrates an embodiment of a graphical user interface (GUI)900 displayed on another embodiment of the UE 100. In this embodiment,the UE 100 includes a smart watch. Using the HM application 108, the UE100 is configured to generate a GUI 900 for display on the display 112.An authorized user is operable to track biosensor data using the UE 100and control certain functions of one or more integrated or externalbiosensors 150 or drug administrative devices 250.

The HM application 108 may be a web-based application supported by acentral application server. For example, the central application servermay be a web server and support the user application via a website. TheUE 100 may then use a web browser or other HTML enabled application toaccess either all or parts of the HM application 108 via the websitesupported by the central application server. The HM application 108 isthen run within the web browser. In another embodiment, the HMapplication 108 is a stand-alone application that is downloaded to theUE 100 and is operable on the UE 100 without access to the web server oronly needs to access the web server for additional information, such asbiosensor data. In another embodiment, the HM application 108 may be amobile application designed for download and use by a mobile phone orother mobile device.

The HM application 108 may generate a GUI 900 on the UE 100. The HMapplication 108 is configured to track and display biosensor data. Forexample, the HM application 108 receives biosensor data from one or morebiosensors 150 and may then upon request generate a GUI 900 thatincludes a graphical display of glucose levels or other biosensor data.The graphical display of the biosensor data may illustrate the data overa requested period of time, such as one day, one week, etc. The HMapplication 108 may issue alerts when biosensor data reaches certainpredetermined thresholds. For example, when the HM application 108determines that a glucose level measurement reaches or exceeds apredetermined high or low threshold, the HM application 108 displays andsounds an alert message. In general, a good range for blood sugar levelsis between 70 milligrams/deciliter (mg/Dl) and 150 mg/Dl. When the sugarlevel are lower than 70 mg/Dl or greater than 150 mg/Dl, the alertmessage may include a request or command to inject insulin by the drugadministrative device 250. The HM application 108 may also trackactivity and generate one or more GUIs 900 that includes an activitytracker display. The activity tracker display may include periods ofrest or sleep and periods of activity along with biosensor data for suchperiods, such as pulse, glucose levels, oxygen levels, temperature,blood pressure, etc.

FIG. 11 illustrates a schematic block diagram of an embodiment of agraphical user interface (GUI) 900 generated by the HM application 108.The HM application 108 may generate the GUI 900, e.g. on the UE 100. TheGUI 900 provides an interface for a user to select a command to controloperation of one or more biosensors 150 integrated with the UE 100 orexternal to the UE 100. For example, a user may select to initiate ascan by a first biosensor 150 by selecting a first scan GUI 1100 or mayselect to initiate a scan by a second biosensor 150 by selecting asecond scan GUI 1102. In another example, a user may select to beginmonitoring by a plurality of biosensors 150 by selecting a BeginMonitoring GUI 1104.

FIG. 12 illustrates a schematic block diagram of an embodiment ofanother graphical user interface (GUI) 900 generated by the HMapplication 108. The HM application 108 may be implemented generate theGUI 900, e.g. on the display 112 of the UE 100, based on biosensor datafrom one or more biosensors 150. The HM application 108 is operable togenerate the GUI 900 to display monitored biosensor data. For example,the GUI 900 may display a Heartbeat Monitor GUI 1200 that tracksdetected heart rate or beats per minute (BPM), e.g. BPM=105. The GUI 900may display a Temperature GUI 1202 that illustrates measured temperatureof a user, and a Blood Glucose Level GUI 1204 that illustrates measuredindicator of blood glucose levels. The GUI 900 may also illustrate anActivate Pump command GUI 1206 to activate a drug administrative device250, such as a drug pump.

The GUI 900 may also illustrate a history of readings of biosensor data.The history may display biosensor data measured over one day, multipledays, one week, one month, one year, or other specified time frame. TheHM application 108 may also generate a display control GUI 1208. A usermay control the display of the GUIs on the UE 100 using the displaycontrol GUI 1208.

FIG. 13 illustrates a schematic block diagram of an embodiment ofanother graphical user interface (GUI) 900 generated by the HMapplication 108. The GUI 900 displays a Settings GUI 1300 for a user todesignate settings for the GUI 900. For example, the Settings GUI 1300may enable a user to select the various biosensor data displayed, suchas heartbeat, temperature, glucose, etc. The HM application 108 may alsoinclude a poll period GUI 1302. The poll period GUI 1302 provides aninterface for a user to select or input a time period or polling periodfor a biosensor measurement or other monitoring.

FIG. 14A illustrates a logical flow diagram of an embodiment of a method1400 of operation of the HM application 108 of the UE 100. In anembodiment, the HM application 108 may generate a GUI 900 for display onthe UE 100 at 1402. The GUI 900 displays one or more commands forcontrolling an integrated or external biosensor 150 at 1404. The HMapplication 108 may receive a user input selecting a command at 1406.The HM application 108 generates a command in response to the user inputat 1408. The HM application 108 initiates transmission of the command toan external biosensor to perform the command or transmits the command toan integrated biosensor to perform the command at 1410.

FIG. 14B illustrates a logical flow diagram of an embodiment of anothermethod 1420 of operation of the HM application 108 of the UE 100. In anembodiment, the HM application 108 receives biosensor data from one ormore integrated or external biosensors at 1422. The HM application 108may generate a GUI 900 that displays biosensor data on the display 112at 1426. The HM application 108 may receive updated biosensor data fromthe one or more biosensors 150. The HM application 108 then updates theGUI 900 on the display 112 based on the updated biosensor data at 1428.The HM application 108 may also transmit biosensor data to thirdparties, such as a doctor's office or pharmacy at 1430. For example, theHM application 108 may generate messages that include requests to refillmedications that are transmitted by the UE 100 to a pharmacy over a widearea network (WAN). In another example, the HM application 108 maygenerate messages that include biosensor data that are transmitted bythe UE 100 to a doctor's hospital over a wide area network (WAN).

Embodiment of a Communication Network

FIG. 15 illustrates a schematic block diagram of an embodiment of anexemplary communication network 1500 in which the devices describedherein may operate. The exemplary communication network 1500 includesone or more networks that are communicatively coupled, such as a widearea network (WAN) 1512, a wired or wireless local area network (LAN)1516, a wireless local area network (WLAN) 1516, and a wireless widearea network (WAN) 1512. The LAN 1518 and the WLANs 1516 may operateinside a home or enterprise environment, such as a medical office,physician office, emergency care center, pharmacy or hospital or otherhealth care provider or business. The wireless WAN 1514 may include, forexample, a 3G or 4G cellular network, a GSM network, a WIMAX network, anEDGE network, a GERAN network, etc. or a satellite network or acombination thereof. The WAN 1512 includes the Internet, serviceprovider network, other type of WAN, or a combination of one or morethereof.

One or more UEs 100 are communicatively coupled to a central applicationserver 1510 by one or more of the exemplary networks in thecommunication network 1500. The central application server 1510 includesa network interface circuit 1502 and a server processing circuit 1504.The network interface circuit 1502 includes an interface for wirelessand/or wired network communications with one or more of the exemplarynetworks in the communication network 1500. The network interfacecircuit 1502 may also include authentication capability that providesauthentication prior to allowing access to some or all of the resourcesof the central application server 1510. The network interface circuit1502 may also include firewall, gateway and proxy server functions.

The central application server 1510 also includes a server processingcircuit 1504 and a memory device 1506. For example, the memory device1506 is a non-transitory, processor readable medium that storesinstructions from the health monitoring server application 1508 whichwhen executed by the server processing circuit 1504, causes the serverprocessing circuit 1504 to perform one or more functions describedherein. In an embodiment, the memory device 1506 stores biosensor datafor a plurality of patients transmitted to the central applicationserver 1510 from the plurality of UE 100.

The central application server 1510 includes a health monitoring serverapplication 1508. The health monitoring server application 1508 isoperable to communicate with the plurality of UE 100. The healthmonitoring server application 1508 may be a web-based applicationsupported by the central application server 1510. For example, thecentral application server 1510 may be a web server and support thehealth monitoring server application 1508 via a website. In anotherembodiment, the health monitoring server application 1508 is astand-alone application that is downloaded to the UE 100 by the centralapplication server 1510 and is operable on the UE 100 without access tothe central application server 1510 or only needs to accesses thecentral application server 1510 for additional information, such asbiosensor data. Using the HM application 108, the plurality of UE 100are configured to track biosensor data and control certain functions ofthe plurality of biosensors 150. In addition, the health monitoringserver application 1508 supports the HM application 108 on one or moreof the plurality of UE 100. The UE 100 may communicate directly with oneor more external biosensors 150 or indirectly through one or morenetworks.

The central application server 1510 may also be operable to communicatewith a third party over the communication network 1220 to providebiosensor data. For example, the HM application 108 may providebiosensor data to a third party health care provider 1540, such as amedical office, hospital, nursing home, etc. For example, the HMapplication 108 may transmit heart rate information or pulse rateinformation or other biosensor data, to the third party health careprovider 1540 over the communication network 1500 as requested orneeded. The HM application 108 may also communicate with a pharmacy 1522to request medication refills or provide biosensor data.

FIG. 16 illustrates a logic flow diagram of an exemplary embodiment of amethod 1600 of operation of the HM application 108 of the UE 100. The HMapplication 108 is configured to receive and monitor biosensor data fromone or more external or integrated biosensors 150 at 1602. For example,the one or more biosensors 150 may detect an indicator of glucoselevels, alcohol levels or other analytes. In addition, the one or morebiosensors 150 may also detect blood pressure, peripheral oxygen (SpO₂)saturation amounts, body temperature, various electrolytes and manycommon blood analytic levels, such as bilirubin amount and sodium andpotassium. The one or more biosensors 150 may also detect blood alcohollevels. The biosensor data is obtained by the HM application 108 andtransmitted by the UE 100 to a third party health care provider 1540 at1604. The third party health care provider 1540 may analyze thebiosensor data and generate a message to the UE 100 in response to thebiosensor data. For example, the third party health care provider 1540may request that a user administer medication or request that the UE 100automatically activate a drug administration device to administermedication at 1606. For example, the biosensor data may include pulserate or blood pressure or other biosensor data. Based on the biosensordata, the third party health care provider 1540 may determine that apatient is having a dangerous allergic reaction and transmits a commandto automatically activate a drug administration device to administer anallergy medication. In another example, the biosensor data indicates aglucose level above a predetermined threshold. The activity monitor mayalso indicate slow or no activity by the user of the UE 100. The thirdparty health care provider 1540 may determine the patient is not able toadminister medication by themselves and so transmits a command to the UE100 to automatically activate a drug administration device to administerinsulin.

The HM application 108 may also generate a request for medication refillto a pharmacy at 1608. The request may be transmitted to a pharmacy 1522by the UE 100 over the communication network 1500. The request may begenerated in response to user input or based on an indicator from thedrug administration device of low medication levels.

Embodiment—PPG Circuit

FIG. 17 illustrates a schematic block diagram illustrating an embodimentof the PPG circuit 300 in more detail. The PPG circuit 300 implementsphotoplethysmography (PPG) techniques for obtaining concentration levelsor indicators of one or more substances in pulsating arterial bloodflow. The PPG circuit 300 includes a light source 1720 having aplurality of light sources, such as LEDs 1722 a-n, configured to emitlight through at least one aperture 1728 a. The PPG circuit 300 isconfigured to direct the emitted light at an outer or epidermal layer ofskin tissue of a patient. The plurality of light sources are configuredto emit light in one or more spectrums, including infrared (IR) light,ultraviolet (UV) light, near IR light or visible light, in response todriver circuit 1718. For example, the biosensor 150 may include a firstLED 1722 a that emits visible light and a second LED 1722 b that emitsinfrared light and a third LED 1722 c that emits UV light, etc. Inanother embodiment, one or more of the light sources 1722 a-n mayinclude tunable LEDs or lasers operable to emit light over one or morefrequencies or ranges of frequencies or spectrums in response to drivercircuit 1718.

In an embodiment, the driver circuit 1718 is configured to control theone or more LEDs 1722 a-n to generate light at one or more frequenciesfor predetermined periods of time. The driver circuit 118 may controlthe LEDs 1722 a-n to operate concurrently or progressively. The drivercircuit 118 is configured to control a power level, emission period andfrequency of emission of the LEDs 1722 a-n. The biosensor 150 is thusconfigured to emit one or more frequencies of light in one or morespectrums that is directed at the surface or epidermal layer of the skintissue of a patient.

The PPG circuit 300 further includes one or more photodetector circuits1730 a-n. For example, a first photodetector circuit 1730 may beconfigured to detect visible light and the second photodetector circuit1730 may be configured to detect IR light. The first photodetectorcircuit 1730 and the second photodetector circuit 130 may also include afirst filter 1760 and a second filter 1762 configured to filter ambientlight and/or scattered light. For example, in some embodiments, onlylight received at an approximately perpendicular angle to the skinsurface of the patient is desired to pass through the filters. The firstphotodetector circuit 1730 and the second photodetector circuit 1732 arecoupled to a first A/D circuit 1738 and a second A/D circuit 1740. TheA/D circuits 1738 and 1740 may also include an amplifier and othercomponents needed to generate the spectral response. In another aspect,the plurality of photodetectors 1730 is coupled in parallel to a singleamplifier and A/D circuit 1738. The light detected by each of thephotodetectors 1730 is thus added and amplified to generate a singlespectral response.

In another embodiment, a single photodetector circuit 1730 may beimplemented operable to detect light over multiple spectrums orfrequency ranges. For example, the photodetector circuit 1730 mayinclude a Digital UV Index/IR/Visible Light Sensor such as Part No.Si1145 from Silicon Labs™.

The one or more photodetector circuits 1730 include a spectrometer orother type of circuit configured to detect an intensity of light as afunction of wavelength or frequency to obtain a spectral response. Theone or more photodetector circuits 1730 detect the intensity of lighteither transmitted through or reflected from tissue of a patient thatenters one or more apertures 1728 b-n of the biosensor 150. For example,the light may be detected from transmissive absorption (e.g., through afingertip or ear lobe) or from reflection (e.g., reflected from aforehead or stomach tissue). The photodetector circuits 1730 a-n thenobtain a spectral response of the detected light by measuring theintensity of light either transmitted or reflected to the photodiodes.

FIG. 18 illustrates a schematic block diagram of another exemplaryembodiment of the the PPG circuit 300. In this embodiment, the PPGcircuit 300 is configured for emitting and detecting light through oneor more optical fibers 1852 a-c. The PPG circuit 300 is opticallycoupled to a plurality of optical fibers 1852 a-c. In an embodiment, theplurality of optical fibers 1852 a-c includes a first optical fiber 1852a optically coupled to the light source 1720. An optical coupler (notshown) to spread the angle of light emitted from the optical fiber 1852a may also be implemented. The optical fiber 1852 a may have a narrowviewing angle such that an insufficient area of skin surface is exposedto the light. An optical coupler 1862 may be used to widen the viewingangle to increase the area of skin surface exposed to the light.

A second optical fiber 1852 b is optically coupled to a firstphotodetector circuit 1730 a and a third optical fiber 1852 c isoptically coupled to the second photodetector circuit 1730 n. Otherconfigurations and numbers of the plurality of optical fibers 1852 mayalso be implemented.

In one aspect, the plurality of optical fibers 1852 is situated withinan outer ear canal to transmit and detect light in the ear canal. Alight collimator 1816, such as a prism, may be used to align a directionof the light emitted from the light source 1720. One or more filters1760, 1762 may optionally be implemented to receive the reflected light1742 from the plurality of optical fibers 1852 b, 1852 c. However, thefilters 1760, 1762 may not be needed as the plurality of optical fibers1852 b, 1852 c may be sufficient to filter ambient light and/orscattered light.

FIG. 19 illustrates a schematic block diagram of an embodiment of thePPG circuit 300 with a plurality of photodetectors 1730. In one aspect,the plurality of photodetectors 1730 are situated in different physicalpositions and orientations in the biosensor 150. For example, at leastfour photodetectors 1730 a, 1730 b, 1730 c and 1730 d are situated inthe biosensor 150 in four different physical positions in a North-Southand East-West orientation or polarity. The output signals of theplurality of photodetectors are coupled in parallel to the amplifier andA/D circuit 1738. The light signals detected by each of thephotodetectors 1730 through an aperture 1728 in the biosensor are addedand amplified to generate a single spectral response. The spectralresponse is thus more robust and less affected by motion artifacts andmovement of the biosensor 150. The LEDs 1722 a-n may be situatedcentrally to the physical position of the plurality of photodetectors1730. The temperature sensor 320 may also be physically situated nearthe PPG circuit 300 to detect temperature through an aperture 1728.

Embodiment—PPG Measurement of Blood Flow

One or more of the embodiments of the biosensor 150 described herein areconfigured to detect a concentration level or indicator of one or moresubstances within blood flow, such as analyte levels, nitric oxidelevels, insulin resistance or insulin response after caloric intake andpredict diabetic risk or diabetic precursors. The biosensor 150 maydetect insulin response, vascular health, cardiovascular sensor,cytochrome P450 proteins (e.g. one or more liver enzymes or reactions),digestion phase 1 and 2 or caloric intake. The biosensor 150 may even beconfigured to detect proteins or other elements or compounds associatedwith cancer. The biosensor 150 may also detect various electrolytes andmany common blood analytic levels, such as bilirubin amount and sodiumand potassium. For example, the biosensor 150 may detect sodium NACLconcentration levels in the arterial blood flow to determinedehydration. The biosensor 150 may also detect blood alcohol levels invivo in the arterial blood flow. Because blood flow to the skin can bemodulated by multiple other physiological systems, the biosensor 150 mayalso be used to monitor breathing, hypovolemia, and other circulatoryconditions. The biosensor 150 may also detect blood pressure, peripheraloxygen (SpO₂ or SaO₂) saturation, heart rate, respiration rate or otherpatient vitals. The biosensor 150 may also be used to detect sleep apneabased on oxygen saturation levels and activity monitoring during sleep.

In use, the biosensor 150 performs PPG techniques using the PPG circuit300 to detect the concentration levels of substances in blood flow. Inone aspect, the biosensor 150 analyzes reflected visible or IR light toobtain a spectrum response such as, the resonance absorption peaks ofthe reflected visible, UV or IR light. The spectrum response includesspectral lines that illustrate an intensity or power or energy at awavelength or range of wavelengths in a spectral region of the detectedlight.

The ratio of the resonance absorption peaks from two differentfrequencies can be calculated and based on the Beer-Lambert law used toobtain various levels of substances in the blood flow. First, thespectral response of a substance or substances in the arterial bloodflow is determined in a controlled environment, so that an absorptioncoefficient α_(g1) can be obtained at a first light wavelength λ₁ and ata second wavelength λ₂. According to the Beer-Lambert law, lightintensity will decrease logarithmically with path length l (such asthrough an artery of length l). Assuming then an initial intensity Ln oflight is passed through a path length l, a concentration C_(g) of asubstance may be determined using the following equations:

At the first wavelength λ₁ , I ₁ =I _(in1)*10^(−(α) ^(g1) ^(C) ^(gw)^(+α) ^(w1) ^(C) ^(w) ^()*l)

At the first wavelength λ₂ , I ₂ =I _(in2)*10^(−(α) ^(g2) ^(C) ^(gw)^(+α) ^(w2) ^(C) ^(w) ^()*l)

wherein:

I_(in1) is the intensity of the initial light at λ₁

I_(in2) is the intensity of the initial light at λ₂

α_(g1) is the absorption coefficient of the substance in arterial bloodat λ₁

α_(g2) is the absorption coefficient of the substance in arterial bloodat λ₂

α_(w1) is the absorption coefficient of arterial blood at λ₁

α_(w2) is the absorption coefficient of arterial blood at λ₂

C_(gw) is the concentration of the substance and arterial blood

C_(w) is the concentration of arterial blood

Then letting R equal:

$R = \frac{\log\; 10\left( \frac{I\; 1}{{Iin}\; 1} \right)}{\log\; 10\left( \frac{I\; 2}{{Iin}\; 2} \right)}$

The concentration of the substance Cg may then be equal to:

${Cg} = {\frac{Cgw}{{Cgw} + {Cw}} = \frac{{\alpha_{w2}R} - \alpha_{w1}}{{\left( {\alpha_{w\; 2} - \alpha_{gw2}} \right)*R} - \left( {\alpha_{w1} - \alpha_{{gw}\; 1}} \right)}}$

The biosensor 150 may thus determine the concentration of varioussubstances in arterial blood using spectroscopy at two differentwavelengths using Beer-Lambert principles.

The biosensor 150 determines concentration of one or more substancesusing Beer-Lambert principles. The biosensor 150 transmits light atleast at a first predetermined wavelength and at a second predeterminedwavelength. The biosensor 150 detects the light (reflected from the skinor transmitted through the skin) and analyzes the spectral response atthe first and second wavelengths to detect an indicator or concentrationlevel of one or more substances in the arterial blood flow. In general,the first predetermined wavelength is selected that has a highabsorption coefficient for the targeted substance while the secondpredetermined wavelength is selected that has a low absorptioncoefficient for the targeted substance. Thus, it is generally desiredthat the spectral response for the first predetermined wavelength have ahigher intensity level than the spectral response for the secondpredetermined wavelength.

In another aspect, the biosensor 150 may transmit light at the firstpredetermined wavelength and in a range of approximately 1 nm to 50 nmaround the first predetermined wavelength. Similarly, the biosensor 150may transmit light at the second predetermined wavelength and in a rangeof approximately 1 nm to 50 nm around the second predeterminedwavelength. The range of wavelengths is determined based on the spectralresponse since a spectral response may extend over a range offrequencies, not a single frequency (i.e., it has a nonzero linewidth).The light that is reflected or transmitted light by the target substancemay by spread over a range of wavelengths rather than just the singlepredetermined wavelength. In addition, the center of the spectralresponse may be shifted from its nominal central wavelength or thepredetermined wavelength. The range of 1 nm to 50 nm is based on thebandwidth of the spectral response line and should include wavelengthswith increased light intensity detected for the targeted substancearound the predetermined wavelength.

The first spectral response of the light over the first range ofwavelengths including the first predetermined wavelength and the secondspectral response of the light over the second range of wavelengthsincluding the second predetermined wavelengths is then generated. Thebiosensor 150 analyzes the first and second spectral responses to detectan indicator or concentration level of one or more substances in thearterial blood flow.

Photoplethysmography (PPG) is used to measure time-dependent volumetricproperties of blood in blood vessels due to the cardiac cycle. Forexample, the heartbeat affects volume of arterial blood flow and theconcentration of absorption levels being measured in the arterial bloodflow. Over a cardiac cycle, pulsating arterial blood changes the volumeof blood flow in an artery. Incident light I_(O) is directed at a tissuesite and a certain amount of light is reflected or transmitted and acertain amount of light is absorbed. At a peak of arterial blood flow orarterial volume, the reflected/transmitted light I_(L) is at a minimumdue to absorption by the venous blood, nonpulsating arterial blood,pulsating arterial blood, other tissue, etc. At a minimum of arterialblood flow or arterial volume during the cardiac cycle, thetransmitted/reflected light I_(H) is at a maximum due to lack ofabsorption from the pulsating arterial blood.

The biosensor 150 is configured to filter the reflected/transmittedlight I_(L) of the pulsating arterial blood from thetransmitted/reflected light I_(H). This filtering isolates the light dueto reflection/transmission of substances in the pulsating arterial bloodfrom the light due to reflection/transmission from venous (or capillary)blood, other tissues, etc. The biosensor 150 may then measure theconcentration levels of one or more substances from thereflected/transmitted light I_(L) in the pulsating arterial blood.Though the above has been described with respect to arterial blood flow,the same principles described herein may be applied to venous bloodflow.

In general, the relative magnitudes of the AC and DC contributions tothe reflected/transmitted light signal I may be used to substantiallydetermine the differences between the diastolic time and the systolicpoints. In this case, the difference between the reflected light I_(L)and reflected light I_(H) corresponds to the AC contribution of thereflected light (e.g. due to the pulsating arterial blood flow). Adifference function may thus be computed to determine the relativemagnitudes of the AC and DC components of the reflected light I todetermine the magnitude of the reflected light I_(L) due to thepulsating arterial blood. The described techniques herein fordetermining the relative magnitudes of the AC and DC contributions isnot intended as limiting. It will be appreciated that other methods maybe employed to isolate or otherwise determine the relative magnitude ofthe light I_(L) due to pulsating arterial blood flow.

FIG. 20 illustrates a schematic diagram of a graph of actual clinicaldata obtained using PPG techniques at a plurality of wavelengths. Thebiosensor 150 emits light having a plurality of wavelengths during ameasurement period. The light at each wavelength (or range ofwavelengths) may be transmitted concurrently or sequentially. Theintensity of the reflected light at each of the wavelengths (or range ofwavelengths) is detected and the spectral response is measured over themeasurement period. The spectral response 2006 for the plurality ofwavelengths obtained using the biosensor in clinical trials is shown inFIG. 20. In this clinical trial, two biosensors 150 attached to twoseparate fingertips of a patient were used to obtain the spectralresponses 2006. The first biosensor 150 obtained the spectral responsefor a wavelength at 940 nm 2010, a wavelength at 660 nm 2012 and awavelength at 390 nm 2014. The second biosensor 150 obtained thespectral response for a wavelength at 940 nm 2016, a wavelength at 592nm 2018 and a wavelength at 468 nm 2020.

In one aspect, the spectral response of each wavelength may be alignedbased on the systolic 2002 and diastolic 2004 points in their spectralresponses. This alignment is useful to associate each spectral responsewith a particular stage or phase of the pulse-induced local pressurewave within the blood vessel (which may mimic the cardiac cycle 2008 andthus include systolic and diastolic stages and sub-stages thereof). Thistemporal alignment helps to determine the absorption measurementsacquired near a systolic point in time of the cardiac cycle 2008 andnear the diastolic point in time of the cardiac cycle 2008 associatedwith the local pressure wave within the patient's blood vessels. Thismeasured local pulse timing information may be useful for properlyinterpreting the absorption measurements in order to determine therelative contributions of the AC and DC components measured by thebiosensor 150. So for one or more wavelengths, the systolic points 2002and diastolic points 2004 in the spectral response are isolated ordetermined. These systolic points 2002 and diastolic points 2004 for theone or more wavelengths may then be aligned as a method to discernconcurrent responses across the one or more wavelengths.

In another embodiment, the systolic points 2002 and diastolic points2004 in the absorbance measurements are temporally correlated to thepulse-driven pressure wave within the arterial blood vessels—which maydiffer from the cardiac cycle. In another embodiment, the biosensor 150may concurrently measure the intensity reflected at each the pluralityof wavelengths. Since the measurements are concurrent, no alignment ofthe spectral responses of the plurality of wavelengths may be necessary.

FIG. 21 illustrates a logical flow diagram of an embodiment of a method2100 of the biosensor 150. In one aspect, the biosensor 150 emits anddetects light at a plurality of predetermined frequencies orwavelengths, such as approximately 940 nm, 660 nm, 390 nm, 592 nm, and468 nm. The light is pulsed for a predetermined period of time (such as100 usec or 200 Hz) sequentially at each predetermined wavelength. Inanother aspect, light may be pulsed in a wavelength range of 1 nm to 50nm around each of the predetermined wavelengths. Then, the spectralresponses are obtained for the plurality of wavelengths at 2102. Thespectral response may be measured over a predetermined period (such as300 usec.). This measurement process is repeated sequentially pulsingthe light and obtaining spectral measurements over a desired measurementperiod, e.g. from 1-2 seconds to 1-2 minutes or 2-3 hours orcontinuously over days or weeks. Because the human pulse is typically onthe order of magnitude of one 1 HZ, typically the time differencesbetween the systolic and diastolic points are on the order of magnitudeof milliseconds or tens of milliseconds or hundreds of milliseconds.Thus, spectral response measurements may be obtained at a frequency ofaround 10-100 Hz over the desired measurement period.

A low pass filter (such as a 5 Hz low pass filter) is applied to thespectral response signal at 2104. The relative contributions of the ACand DC components are obtained I_(AC+DC) and I_(AC). A peak detectionalgorithm is applied to determine the systolic and diastolic points at2106. Beer Lambert equations are applied as described below at 2108. Forexample, the L_(λ) values are then calculated for one or more of thewavelengths λ, wherein the L_(λ) values for a wavelength equals:

$L_{\lambda} = {{Log}\; 10\left( \frac{{IAC} + {DC}}{IDC} \right)}$

wherein I_(AC+DC) is the intensity of the detected light with AC and DCcomponents and I_(DC) is the intensity of the detected light with the ACfiltered by the low pass filter at 2110. The value L_(λ) isolates thespectral response due to pulsating arterial blood flow, e.g. the ACcomponent of the spectral response.

A ratio R of the L_(λ) values at two wavelengths may then be determined.For example,

${{Ratio}\mspace{14mu} R} = \frac{L\lambda 1}{L\lambda 2}$

The L_(λ) values and Ratio R may be determined for one or more of thepredetermined measurement periods over a desired time period, e.g. from1-2 seconds to 1-2 minutes or 2-3 hours or continuously over days orweeks to monitor the values. The L_(λ) values and Ratio R may be used todetermine concentration levels of one or more substances in the arterialblood flow at 2112 as well as patient vitals, such as oxygen saturationSpO₂, heart rate, respiration rate, etc.

Embodiment—Determination of Indicators or Concentration Levels of One orMore Substances

In one aspect, based on unexpected results from clinical trials, it wasdetermined that a ratio R_(390,940) obtained at approximately L_(λ1)=390nm and L_(λ2)=940 is useful as a predictor or indicator of diabetic riskor diabetes. For example, during experimental clinical trials, spectralresponses were obtained during predetermined measurement periods over a1-2 minute time period at 390 nm and 940 nm. An R_(390,940) value wasobtained based on the spectral responses measured during a plurality ofthe predetermined measurement periods over the 1-2 minute time period.From the unexpected results of the clinical trials, an average or meanR_(390,940) value of less than 1 (e.g., approximately 0.5) indicatedthat a person has diabetes or early onset of diabetes. An average ormean R_(390,940) value of 2 or above indicated that a person has a lowerrisk of a diabetes diagnosis. An average or mean R_(390,940) value inthe 5-6 range indicated no current risk of diabetes. The R_(390,940)value determined using L_(λ1)=390 nm and L_(λ2=940) was thus anindicator of diabetic risk and diabetes. Thus, based on the clinicaltrials, a non-invasive, quick 1-2 minute test produced an indicator ofdiabetes or diabetic risk in a person.

In particular, in unexpected results, it is believed that nitric oxideNO levels in the arterial blood flow is being measured at least in partby the biosensor 150 at λ1=390 nm. Since NO is partly in a gaseous formin blood vessels (prior to adhesion to hemoglobin), the total NOconcentration levels of in vitro blood samples, e.g. from a fingerprick, are not detected as the gas dissipates. Thus, the biosensor 150measurements to determine the L_(390 nm) values are the first time NOconcentration levels in arterial blood flow have been measured directlyin vivo. In clinical trials performed as described further herein, inunexpected results, it seems that the NO levels are an indication ofinsulin response in the blood as well as concentration levels of insulinand/or glucose levels in the blood. The L_(λ1=390 nm) and R valueobtained from L_(λ1=390 nm) are thus an indicator of blood glucoselevels, insulin response and diabetic risk as well as vascular health.These unexpected results have advantages in early detection of diabeticrisk and easier, non-invasive monitoring of insulin resistance andglucose levels as well as vascular health and other conditions. Theseresults are discussed in more detail herein with illustrativeexperimental data.

The biosensor 150 may also function as a pulse oximeter using similarprinciples under Beer-lambert law to determine pulse and oxygensaturation levels in pulsating arterial flow. For example, a firstwavelength at approximately 940 nm and a second wavelength atapproximately 660 nm may be used to determine oxygen saturation levels.

The biosensor 150 may also be used to determine alcohol levels in theblood using wavelengths at approximately 390 nm and/or 468 nm. Inanother embodiment, an R_(468,940) value for at leastL_(468 nm)/L_(940 nm) may be used as a liver enzyme indicator, e.g. P450enzyme indicator. In another embodiment, an R_(592,940) value for atleast L_(592 nm)/L_(940 nm) may be used as a digestive indicator tomeasure digestive responses, such as phase 1 and phase 2 digestivestages. The biosensor 150 may also detect other types of electrolytes oranalytes, such as sodium and potassium, using similar PPG techniques. Inanother aspect, the biosensor 150 may detect which blood cell levels inarterial blood flow using similar PPG techniques.

In another aspect, abnormal cells or proteins or compounds that arepresent or have higher concentrations in the blood with persons havingcancer, may be detected using similar PPG techniques described herein atone or more other wavelengths. Thus, cancer risk may then be obtainedthrough non-invasive testing by the biosensor 150.

Since the biosensor 150 may operate in multiple frequencies, varioushealth monitoring tests may be performed concurrently and continuously.These tests may be performed throughout a hospital stay or may benon-invasively and quickly and easily obtained using the biosensor 150in a physician's office or other clinical setting or at home. These andother aspects of the biosensor 150 are described in more detail hereinwith clinical trial results.

FIG. 22 illustrates a logical flow diagram of an embodiment of a method2200 of determining concentration levels of one or more substances inmore detail. The biosensor 150 obtains a first spectral response signalincluding a first wavelength and a second response signal including asecond wavelength at 2202. In general, the first wavelength is selectedthat has a high absorption coefficient for the targeted substance whilethe second wavelength is selected that has a low absorption coefficientfor the targeted substance. Thus, it is generally desired that thespectral response for the first predetermined wavelength have a higherintensity level than the spectral response for the second predeterminedwavelength.

Each of the spectral response signals includes AC and DC componentsI_(AC+DC). A low pass filter is applied to the spectral response signalsI_(AC+DC) to isolate the DC component of the first and second spectralresponse signals I_(DC) at 2204. The AC fluctuation is due to thepulsatile expansion of the arteriolar bed due to the volume increase inarterial blood. In order to measure the AC fluctuation, measurements aretaken at different times and a peak detection algorithm or other meansis used to determine or isolate the diastolic point and the systolicpoint of the spectral response at 2206. The systolic and diastolicmeasurements are compared in order to compute the aforementioned Rratio. For example, a logarithmic function may be applied to the ratioof I_(AC+DC) and I_(DC) to obtain an L value for the first wavelengthL_(λ1) at 2208 and for the second wavelength L_(λ2) at 2210. The ratio Rof the L_(λ) values may then be calculated at 2212. The L values andRatio R may be used to determine concentration levels of one or moresubstances in the arterial blood flow at 2214.

In one aspect, the biosensor 150 may include a broad spectrum lightsource 1020, such as a white light to infrared (IR) or near IR LED 1022,that emits light with wavelengths from e.g. 350 nm to 2500 nm. Broadspectrum light sources with different ranges may be implemented. In anaspect, a broad spectrum light source with a range across 100 nmwavelengths to 2000 nm range of wavelengths in the visible, IR and/or UVfrequencies. For example, a broadband tungsten light source forspectroscopy may be used. The spectral response of the reflected lightis then measured across the wavelengths in the broad spectrum, e.g. from350 nm to 2500 nm, concurrently. In an aspect, a charge coupled device(CCD) spectrometer 1030 may be configured to measure the spectralresponse of the detected light over the broad spectrum.

The spectral response of the reflected light is analyzed for a pluralityof wavelengths, e.g. at 10 nm to 15 nm to 20 nm, incremental wavelengthsacross the wavelengths from 10 nm to 2500 nm. For example, theprocessing described with respect to FIG. 21 is performed at theplurality of wavelengths. In one aspect, the L values are calculated atincremental wavelengths, such as at nm or 1.5 nm or 2 nm incrementalwavelengths. This process may be used to determine one or morewavelengths or ranges of wavelengths useful in detection for one or moresubstances in the arterial blood flow. For example, a spectral responsearound a wavelength of 500 nm may have a higher intensity. Trials maythen be conducted to determine the one or more substances in the bloodthat generates this spectral response. In another embodiment, a knownsubstance may be present in the blood and the spectral response acrossthe broad spectrum is then analyzed to determine a pattern orcorrelation of intensities of wavelengths in the spectral response tothe known substance. For example, a pattern of intensities ofwavelengths across a range of wavelengths may indicate the presence of asubstance. The intensities of the wavelengths may then be analyzed todetermine concentration levels of the substance as described in moredetail herein.

In another embodiment, the spectral response is analyzed at a set ofpredetermined wavelengths (or a range of 1 nm to 50 nm including eachpredetermined wavelength). The L values are calculated for the set ofpredetermined wavelengths using the analyzed spectral responses. Theconcentration levels of one or more substances may then be determinedbased on absorption coefficients for the one or more substances at eachof the predetermined wavelengths. The concentration levels of aplurality of substances may be determined using the spectral response ofa plurality of frequencies at 2214. The biosensor 150 may thus be usedto detect a plurality of substances based on data obtained during asingle measurement period. The biosensor 150 may thus perform a bloodpanel analysis based on in vivo arterial blood flow in a relativelyshort measurement period of 1-5 minutes. The blood panel analysis may beperformed in a physician's office to determine results of the test whilethe patient is in the office. The biosensor 150 may thus provide bloodpanel analysis results in a 1-5 minute measurement period without a needfor blood samples and lab tests that may take hours or days or weeks toobtain.

FIG. 23A illustrates a graph of an embodiment of an output of a broadspectrum light source. The relative light intensity or power output ofthe broad spectrum light source is shown versus wavelength of the outputlight Jo. The light intensity or power of the output light extends fromwavelengths of approximately 350 nm to approximately 2500 nm. A broadspectrum light source emits light with power across the wavelengths from350 nm to 2500 nm. Broad spectrum light sources with different rangesmay be implemented. In an aspect, a broad spectrum light source with arange across 100 nm wavelengths to 2000 nm range of wavelengths in thevisible, IR and/or UV frequencies.

FIG. 23B illustrates a graph with an embodiment of an exemplary spectralresponse of detected light 2304 across a broad spectrum, e.g. fromapproximately 10 nm to 2000 nm. In one aspect, the spectral response ofthe detected light 2304 may be analyzed at a plurality of wavelengths,e.g. at a set of predetermined wavelengths or at incrementalwavelengths. In another aspect, the spectral response of wavelengthswith a detected intensity or power exceeding a predetermined thresholdmay be analyzed. For example, in the graph shown in FIG. 23B, thespectral response at wavelengths of 200 nm, 680 nm and 990 nm (andranges of +/−20 to 50 nm around these wavelengths) exceeding a relativeintensity threshold of 20000 may be analyzed.

FIG. 24 illustrates a schematic block diagram of an embodiment of amethod 2400 for determining concentration levels or indicators ofsubstances in pulsating blood flow in more detail. The biosensor 150obtains a spectral response signal at a first wavelength and at a secondwavelength at 2402. The spectral response signal includes AC and DCcomponents IAC+DC. A low pass filter is applied to the spectral responsesignal IAC+DC to isolate the DC component 2406 of the spectral responsesignal at each wavelength at 2404. The AC fluctuation is due to thepulsatile expansion of the arteriolar bed due to the volume increase inarterial blood. In order to measure the AC fluctuation, measurements aretaken at different times and a peak detection algorithm or other meansis used to determine the diastolic point and the systolic point of thespectral response at 2408. The systolic and diastolic measurements arecompared in order to compute the L values using Beer-Lambert equationsat 2410. For example, a logarithmic function may be applied to the ratioof IAC+DC and I_(DC) to obtain an L value for the first wavelengthL_(λ1) and for the second wavelength L_(λ2). The ratio R of the firstwavelength L_(λ1) and for the second wavelength L_(λ2) may then becalculated at 2412. Beer-Lambert principles are applied to the ratios Rat 2414. For example, when multiple frequencies are used to determine aconcentration level of one or more substances, the linear functiondescribed herein are applied at 2416, and the one or more concentrationlevels of the substances or analytes are determined at 2418.

In an embodiment, a substances or analyte may be attached in the bloodstream to one or more hemoglobin compounds. The concentration level ofthe hemoglobin compounds may then need to be subtracted from theconcentration level of the substance to isolate the concentration levelof the substance from the hemoglobin compounds. For example, nitricoxide (NO) is found in the blood stream in a gaseous form and alsoattached to hemoglobin compounds. Thus, the measurements at L_(390 nm)to detect nitric oxide may include a concentration level of thehemoglobin compounds as well as nitric oxide.

The hemoglobin compound concentration levels may be determined andsubtracted to isolate the concentration level of the substance at 2420.The hemoglobin compounds include, e.g., Oxyhemoglobin [HbO2],Carboxyhemoglobin [HbCO], Methemoglobin [HbMet], and reduced hemoglobinfractions [RHb]. The biosensor 150 may control the PPG circuit 300 todetect the total concentration of the hemoglobin compounds using acenter frequency of 660 nm and a range of 1 nm to 50 nm. A method fordetermining the relative concentration or composition of different kindsof hemoglobin contained in blood is described in more detail in U.S.Pat. No. 6,104,938 issued on Aug. 15, 2000, which is hereby incorporatedby reference herein.

Various unexpected results were determined from clinical trials usingthe biosensor 150. In one aspect, based on the clinical trials, an Rvalue obtained from the ratio L_(λ1=390 nm) and L_(λ2=940 nm) was foundto be a predictor or indicator of diabetic risk or diabetes as describedin more detail herein. In another aspect, based on the clinical trials,the R value obtained from the ratio of L_(468 nm)/L_(940 nm) wasidentified as an indicator of the liver enzyme marker P450. In anotheraspect, based on the clinical trials, the R value obtained from theratio of L_(592 nm)/L_(940 nm) was identified as an indicator ofdigestion phases, such as phase 1 and phase 2, in the arterial bloodflow. In another aspect, the R value from the ratio ofL_(660 nm)/L_(940 nm) was found to be an indicator of oxygen saturationlevels SpO₂ in the arterial blood flow. In another aspect, it wasdetermined that the biosensor 150 may determine alcohol levels in theblood using spectral responses for wavelengths at 390 and/or 468 nm. Ingeneral, the second wavelength of 940 nm is selected because it has alow absorption coefficient for the targeted substances described herein.Thus, another wavelength other than 940 nm with a low absorptioncoefficient for the targeted substances (e.g. at least less than 25% ofthe absorption coefficient of the targeted substance for the firstwavelength) may be used instead. For example, the second wavelength of940 nm may be replaced with 860 nm that has a low absorption coefficientfor the targeted substances. In another aspect, the second wavelength of940 nm may be replaced with other wavelengths, e.g. in the IR range,that have a low absorption coefficient for the targeted substances. Ingeneral, it is desired that the spectral response for the firstpredetermined wavelength have a higher intensity level than the spectralresponse for the second predetermined wavelength.

In another aspect, it was determined that other proteins or compounds,such as those present or with higher concentrations in the blood withpersons having cancer, may be detected using similar PPG techniquesdescribed herein with biosensor 150 at one or more other wavelengths.Cancer risk may then be determined using non-invasive testing over ashort measurement period of 1-10 minutes. Since the biosensor mayoperate in multiple frequencies, various health monitoring tests may beperformed concurrently. For example, the biosensor 150 may measure fordiabetic risk, liver enzymes, alcohol levels, cancer risk or presence ofother analytes within a same measurement period using PPG techniques.

FIG. 25 illustrates a logical flow diagram of an exemplary method 2500to determine an absorption coefficients of a substance at a wavelengthλ. The concentration level of a substance in arterial blood is obtainedusing a known method at 2502. For example, blood may be extracted atpredetermined intervals during a time period and a blood gas analyzermay be used to measure a concentration level of a substance. Thebiosensor 150 emits light at a wavelength (and in one aspect for a rangeof 1 nm-50 nm around the wavelength) and detects a spectral response forthe wavelength (and in one aspect for a range of 1 nm-50 nm around thewavelength) at 2504. The spectral response for the predeterminedwavelength is analyzed at 2506. The intensity of the detected light isdetermined. The intensity of the detected light is compared to the knownconcentration level of the substance at 2508. The absorption coefficientfor the substance may then be determined using the Beer-Lambertequations described herein at 2510.

The above process may be repeated at one or more other frequencies at2512. For example, as described herein, the spectral analysis over arange or at multiple frequencies may be analyzed to determine one ormore frequencies with a higher intensity or power level in response to aconcentration level or presence of the substance. Thus, one or morefrequencies may be analyzed and identified for detection of thesubstance, and the absorption coefficient for the substance determinedat the one or more frequencies.

In another embodiment, the concentration level of a substance may beobtained from predetermined values obtained through experimentation. Forexample, in a calibration phase, a correlation table may be compiledthrough experimentation that includes light intensity values I_(1-n) atone or more wavelengths λ_(1-n) and a corresponding known concentrationlevel for the substance for the light intensity values. In use, thebiosensor 150 detects a spectral response and determines the lightintensity values I_(1-n) at one or more wavelengths λ_(1-n). Thebiosensor 150 then looks up the detected light intensity values I_(1-n)in the correlation table to determine the concentration level of thesubstance.

FIG. 26 illustrates a schematic drawing of another exemplary embodimentof results of clinical data 2600 obtained using an embodiment of thebiosensor 150 from a second patient. The second patient is a 59 year oldmale with a known diagnosis of Type 2 diabetes. At predetermined timeperiods of about 15 minutes, blood glucose level (BGL) was measuredusing a known method of a blood glucose meter (BGM) using blood fromfinger pricks. The BGM glucose measurements 2604 are plotted. Theplotted measurements were interpolated to generate a polynomial 2606showing the approximate BGM glucose measurements over time in mG/DLunits. The biosensor 150 obtained measurements over the same time periodto derive the Ratio R for approximately L_(390 nm)/L_(940 nm) 2602, asshown on the graph as well.

In this clinical trial, the base insulin resistance factor measuredprior to eating has a low baseline value of about 0.5 indicating adiabetic condition. In unexpected results, the base insulin resistancefactor or R value for L_(390 nm)/L_(940 nm) of less than 1 (in an Rvalue range of 0-8) thus seems to indicate a diabetic condition from theclinical trial results. After consumption of a high sugar substance,insulin response 2610 is seen after about 7 minutes. The blood glucoselevels may be obtained from the R values using the graph 2600 or asimilar calibration table that correlates the R value with known BGLmeasurements for the patient. The calibration table may be generated fora specific patient or may be generated from a sample of a generalpopulation. It is determined that the R values should correlate tosimilar BGL measurements across a general population. Thus, thecalibration table may be generated from testing of a sample of a generalpopulation.

From the unexpected results of the clinical trials, an R value of lessthan 1 (in an R value range of 0-8) indicated that a person has diabetesor early onset of diabetes. An R value of 5 (in an R value range of 0-8)or above indicated that a person has no diabetic condition. For example,as shown in graph 2608, the base insulin resistance factor measuredusing an R value of approximately L_(390 nm)/L_(940 nm) has generally anaverage value greater than 5 in the first patient without a diabetesdiagnosis. The base insulin resistance factor measured using an R valueof approximately L_(390 nm)/L_(940 nm) was generally an average valueless than 1 (in an R value range from 0-8) in the other patients with adiabetes diagnosis of either Type 1 or Type II. The base insulinresistance factor measured using an R value in the 1-2 (in an R valuerange from 0-8) range indicated a high risk of diabetes and need forfurther testing.

It seems that the L_(390 nm) is measuring NO levels in the arterialblood flow. As insulin is generated in the body, it reacts with bloodvessels to generate NO gas. The NO gas bonds to hemoglobin and istransported in the blood stream. The NO is thus a good indicator of abase insulin resistance factor after fasting and an insulin responseafter caloric intake.

From the clinical trials, it seems that the NO levels are reflected inthe R values obtained from L_(390 nm)/L_(940 nm). Based on the clinicaltrials and R values obtained in the clinical trials, it is determinedthat a base insulin resistance factor of less than 1 corresponds to anNO concentration level of at least less than 25% of average NO levels.For example, average NO levels are determined by sampling a generalpopulation of persons without diabetes or other health conditionsaffecting NO levels. From the clinical trials, an R value correlating toa base insulin factor of less than 1 indicates that the NO levels are ina range of 25% to 50% less than average NO levels. After fasting, aperson with a diabetic condition will have low NO concentration levelsthat are at least 25% less than average NO levels due to the low levelof insulin in the blood. Thus, an NO concentration level of at leastless than 25% of normal ranges of NO concentration levels indicates adiabetic condition (e.g., the NO levels corresponding to R value lessthan 1 in this clinical trial). Thus, a base insulin resistance factorof less than 1 correlates to at least less than 25% of average NO levelsof a sample population and indicates a diabetic condition.

Based on the clinical trials and R values obtained in the clinicaltrials, it is determined that a base insulin resistance factor in therange of 2-8 corresponds to average NO concentration levels. Thus, abase insulin resistance factor (e.g. in the range of 2-8) correlates toan average NO level of a sample population and little to no diabeticrisk.

Based on these unexpected results, in one aspect, the biosensor 150 maydisplay or transmit, e.g. to a user device or monitoring station, orotherwise output an indicator of the diabetic risk of a patient based onthe R value. For example, the biosensor 150 may output no diabetic riskbased on an obtained R value for a patient of 5 or greater. In anotheraspect, the biosensor 150 may output low diabetic risk based on anobtained R value of 2-5. In another aspect, the biosensor 150 may outputhigh diabetic risk based on an obtained R values of 1-2. In anotheraspect, the biosensor 150 may output diabetic condition detected basedon an R value less than one. In the clinical trials herein, the R valuewas in a range of 0-8. Other ranges, weights or functions derived usingthe R value described herein may be implemented that changes thenumerical value of the R values described herein or the range of the Rvalues described herein. In general, from the results obtained herein,an R value corresponding to at least the lower 10% of the R value rangeindicates a diabetic condition, an R value in the lower 10% to 25% ofthe R value range indicates a high risk of diabetes, an R value in the25% to 60% range indicates a low risk of diabetes, and an R valuegreater than 60% indicates no diabetic condition.

The R value of L_(390 nm)/L_(940 nm) may be non-invasively and quicklyand easily obtained using the biosensor 150 in a physician's office orother clinical setting or at home. In one aspect, the R value may beused to determine whether further testing for diabetes needs to beperformed. For example, upon detection of a low R value of less than 1,a clinician may then determine to perform further testing andmonitoring, e.g. using glucose ingestion tests over a longer period oftime or using the biosensor 150 over a longer period of time or othertype of testing.

Embodiment—Blood Alcohol Level Measurements

FIG. 27 illustrates a schematic drawing of another exemplary embodimentof results of clinical data 2700 obtained using an embodiment of thebiosensor 150 from a third patient. In this trial, the third patient wasa 55 year old male that ingested a shot of whiskey at approximately 7seconds. The biosensor 150 was used to measure an indicator of bloodalcohol levels over a measurement period of approximately 271 secondsusing a wavelength of approximately 468 nm. The graph illustrates thevalues obtained for ratio R=L_(468 nm)/L_(940 nm) 2702 over themeasurement period. The biosensor 150 was able to detect the increase inthe blood alcohol levels over the measurement period. The ratio R values2702 may be correlated with blood alcohol levels using a table or graphthat associates the R values 2702 with blood alcohol levels. Forexample, the table or graph may be obtained through blood alcohol levelsmeasured from blood drawn at preset intervals (such as every 1-5minutes) during a measurement period (such as 1-5 hours) andinterpolating the resulting measurements. The interpolated measurementsare then associated with the measured ratio R values 2702 over the samemeasurement period. In general, the ratio R values 2702 are consistentwith an approximate measured blood alcohol level in subsequent clinicaltrials for a patient. The calibration of measured blood alcohol levelsto ratio R values 2702 may thus only be performed once for a patient. Inanother aspect, the calibration table may be generated using testing ofa sample of a general population. It is determined that the R valuesshould correlate to similar BAL measurements across a generalpopulation. Thus, the calibration table may be generated from testing ofa sample of a general population.

In unexpected results, concentration levels of a liver enzyme calledcytochrome P450 Oxidase (P450) that is generated in the presence ofalcohol may be measured by the biosensor 150. The spectral responsearound the wavelength at approximately 468 nm seems to track theconcentration levels of the liver enzyme P450. The liver enzyme isgenerated to react with various substances and may be generated inresponse to alcohol levels. Thus, the measurement of the spectralresponse for the wavelength at approximately 468 nm may indicate bloodalcohol levels and/or concentration levels of P450.

Embodiment—Digestive Stage and Caloric Intake Measurements

FIG. 28 illustrates a schematic drawing of another exemplary embodimentof results of clinical data 2800 obtained using the biosensor 150 from afourth patient. In this trial, the fourth patient ingested whiskey atapproximately 13 seconds. The biosensor 150 was used to measure thedigestive stages over a measurement period of approximately 37 minutesusing a wavelength of approximately 390 nm to track the blood glucoselevels. The graph illustrates the values for L_(390 nm) 2802 obtainedover the measurement period. The biosensor 150 was able to detect thedigestive stage 1 2804 and digestive stage 2 2806 based on the obtainedvalues for L_(390 nm). The first digestive stage 1 2804 is indicated byan initial spike around 20 seconds as blood rushes to the stomach to aidin digestion. The second digestive stage 2 is indicated by a later, moreprolonged increase in blood glucose levels between 60 and 180 seconds.

Based on the insulin response and BGL measurements, a calibration ofcaloric intake may be performed for a patient. For example, knowncaloric intakes may be correlated with insulin response in phase 1 andphase 2 digestions measured using values for L_(390 nm) 2802. In anotheraspect, the calibration table may be generated using testing of a sampleof a general population. It is determined that the R values usingL_(390 nm) 2802 and, e.g., L_(940 nm) should correlate to similarcaloric intake measurements across a general population. Thus, thecalibration table may be generated from testing of a sample of a generalpopulation.

Embodiment—Measurements of Other Substances

Using similar principles described herein, the biosensor 150 may measureconcentration levels or indicators of other substances in pulsatingblood flow. For example, absorption coefficients for one or morefrequencies that have an intensity level responsive to concentrationlevel of substance may be determined. The biosensor 150 may then detectthe substance at the determined one or more frequencies as describedherein and determine the concentration levels using the Beer-Lambertprinciples and the absorption coefficients. The L values and R valuesmay be calculated based on the obtained spectral response. In oneaspect, the biosensor 150 may detect various electrolyte concentrationlevels or blood analyte levels, such as bilirubin (using L_(460 nm)) andiron (using L_(510 nm), L_(651 nm), L_(300 nm)) and potassium (usingL_(550 nm)).

In another aspect, the biosensor 150 may detect sodium chloride NACL(using L_(450 nm)) concentration levels in the arterial blood flow anddetermine dehydration level. The biosensor 150 may then output adetermination of level of dehydration based on the detected NACLconcentration levels.

In yet another aspect, the biosensor 150 may be configured to detectproteins or abnormal cells or other elements or compounds associatedwith cancer. The biosensor 150 may measure concentration levels orindicators of other substances in pulsating blood flow using similarprinciples described herein.

For example, the value L_(λ1) is determined from a spectral response ofa wavelength with a high absorption coefficient for the targetedsubstance. The value L_(λ2) is determined from a spectral response ofthe wavelength with a low absorption coefficient for the targetedsubstance. The ratio R_(λ1, λ2) is determined from the value L_(λ1) andthe value L_(λ2). A calibration table may be generated using testing ofa sample of a general population that correlates values of the ratioR_(λ1, λ2) to concentration levels of the target substance. Then theconcentration level of the targeted substance may be determined usingthe calibration table and the measured values for the ratio R_(λ1, λ2).

Embodiment—Detection of Types of Cells

The biosensor 150 may detect concentration levels of different types ofcells in arterial blood flow. For example, the biosensor 150 may detectthe various types of white blood cells based on the spectral response ofthe wavelengths, e.g. using one or more wavelengths shown in Table 1below.

TABLE 1 Detection of White Blood Cells White Blood Spectral AbsorptionCell Type Diameter Color Wavelengths Neutrophil 10-12 um Pink-Red,Red-660 nm Blue, White Blue-470 nm Green-580 nm Eosinophil 10-12 um Pink660 nm, 470 nm, 580 nm Orange 600 nm Basophil 12-15 um Blue 470 nmLymphocyte  7-15 um 633 nm Monocyte 15-30 um 580 nm

The biosensor 150 may detect a color or color change of the blood due toan increase or decrease in white blood cells using one or morewavelengths described in Table 1. Based on the detected color or colorchange of the blood, the biosensor 150 may output an alert to a presenceof an infection. For example, the biosensor 150 monitors the color ofthe blood. When it detects a color change indicating an increase inwhite blood cells, the biosensor determines whether this color changemeets a predetermined threshold indicating a presence of an infection.The predetermined threshold may include a color scale and/or length oftime of color change. When the color change reaches the predeterminedthreshold, the biosensor 150 transmits or displays an alert to indicatea presence of an infection.

In another aspect, the biosensor 150 may detect white blood cells fromspectral responses at one or more wavelengths. Due to the larger size ofthe white blood cells from red blood cells, the presence of white bloodcells in the blood affects the spectral width and shape of a spectralresponse.

FIG. 29 illustrates an exemplary graph 2900 of spectral responses of aplurality of wavelengths from clinical data using the biosensor 150. Inthis embodiment, the spectral response of a plurality of wavelengths wasmeasured using the biosensor 150 over a measurement period of almost 600seconds or approximately 10 minutes. The graph 2900 illustrates the Lvalues calculated from the spectral response for a first wavelength 2902of approximately 940 nm, the spectral response for a second wavelength2904 of approximately 660 nm and the spectral response for a thirdwavelength 2906 of approximately 390 nm obtained from a first biosensor150 measuring reflected light from a first fingertip of a patient. Thegraph further illustrates the spectral response for a fourth wavelength2910 of approximately 592 nm and a fifth wavelength 2914 ofapproximately 468 nm and the spectral response 1408 again at 940 nmobtained from a second biosensor measuring reflected light from a secondfingertip of a patient. The spectral responses are temporally alignedusing the systolic and diastolic points. Though two biosensors were usedto obtain the spectral responses in this clinical trial, a singlebiosensor 150 may also be configured to obtain the spectral responses ofthe plurality of wavelengths.

Due to the size of white blood cells, the presence of the white bloodcells in the blood affects the spectral width and shape of a spectralresponse at one or more wavelengths. In one aspect, from L values 2920shown for the spectral response at 660 nm 2904, the width and shape ofthe spectral response is affected by the presence of white blood cells.For example, the width and shape of L_(660 nm) between 250 and 270seconds has a different shape and width of L_(660 nm) between 300 and320 seconds in the graph 2900. The differences in the width and shape ofthe spectral response may be used to determine a concentration level ofwhite blood cells or change in concentration level of white blood cellsin the blood.

In another example, the spectral responses may be used to determine apresence of infection from a level of neutrophils or neutrophilic whiteblood cells in arterial blood flow. The concentration of neutrophilsincreases in the presence of an infection. The neutrophil particles havea different color and size from red blood cells. The biosensor 150 maydetermine an increase in concentration of neutrophil cells in responseto a change in color of the blood. In addition, the biosensor 150 maydetermine an increase in concentration of neutrophil cells in responseto a change in a pattern of the spectral response (L value and/or Rvalue) due to a change in size of particles in the blood. The biosensor150 may use a combination of both a change in color and change in apattern of the spectral response (L value and/or R value) to determine aconcentration of neutrophils.

FIG. 30 illustrates an exemplary graph 3000 of spectral responses of aplurality of wavelengths from clinical data using the biosensor 150. Thegraph 3000 illustrates use of the spectral response to determine a levelof arterial dilation or vasodilation. Vasodilation refers to thewidening of blood vessels. It results from relaxation of smooth musclecells within the vessel walls. A substance that causes dilation of bloodvessels by promoting the relaxation of vascular smooth muscle arereferred to as vasodilators. Chemical vasodilators include hydralazine,nitroglycerin, nitroprusside, nesiritide, and trimethaphan.

The spectral response in graph 3000 illustrates an increase in intensityof the spectral response at approximately 35 minutes in arterial bloodflow. The spectral responses are from wavelengths in the infrared (IR)range and in the ultraviolet (UV) range from clinical data using thebiosensor 150. The spectral responses may be used to obtain a level ofdilation of the arteries of a patient. For example, upon ingestion offood, blood gases such as NO are released and cause dilation of thevessels. The infrared (IR) spectral measurement increases in intensityas shown in graph 3000 at about 35 minutes due to increased blood flowthrough the dilated arteries. The increase in a spectral response of IRlight 3004 may be measured and mapped to a level of dilation of thearteries. A spectral response of UV light 3002 may also be measured andmapped to a level of dilation as seen in the graph 3000 at about 35minutes. The level of vasodilation may thus be measured using thespectral responses of light in the IR or UV range.

FIG. 31 illustrates an exemplary graph 3100 of spectral responses of aplurality of wavelengths from clinical data using the biosensor 150. Thespectral responses may be used to determine the presence andconcentration of various organisms in arterial blood flow. Due to thesize and shape of various organisms, the presence of the organisms inthe blood affects the spectral width and shape of a spectral response atone or more wavelengths. In one aspect, from L values shown for thespectral response at 660 nm 3104, the width and shape of the spectralresponse is affected by the presence of white blood cells. For example,the width and shape of L_(660 nm) between 290 and 320 seconds has adifferent shape and width. The differences in the width and shape of thespectral response may be used to determine a presence of an organism, aconcentration level of an organism or change in concentration level ofan organism in the arterial blood flow.

For example, a test is performed on blood with a known concentration ofa certain virus. The spectral responses of a plurality of wavelengths ofarterial blood flow are detected with the PPG circuit 300. The spectralresponses are analyzed to determine one that is affected by the presenceof the virus. The spectral response of the selected wavelength isanalyzed to determine different patterns in shape and width indicatingthe presence of the virus. The pattern of the spectral response of theselected wavelength may then be mapped to the known concentration of thecertain virus. This mapping may be performed for different knownconcentrations of the virus to generate a mapping table. The presenceand/or concentration level of the virus in arterial blood flow ofunknown samples may then be determined from the spectral response of theselected wavelength. This process may be performed for other types oforganisms as well.

The PPG circuit 300 may thus be used to determine a concentration levelof one or more substances or types of cells or organisms in arterialblood flow using the spectral responses. Such substances include but arenot limited to natural and artificial occurring vasodilators, enzymes,and proteins.

The UE 100 communicates with one or more external biosensors, such as anear biosensor and a skin biosensor, to collect and track biosensor data.The UE 100 may also include integrated biosensors.

A processing circuit includes at least one processing device, such as amicroprocessor, micro-controller, digital signal processor,microcomputer, central processing unit, field programmable gate array,programmable logic device, state machine, logic circuitry, analogcircuitry, digital circuitry, and/or any device that manipulates signals(analog and/or digital) based on hard coding of the circuitry and/oroperational instructions. A memory is a non-transitory memory device andmay be an internal memory or an external memory, and the memory may be asingle memory device or a plurality of memory devices. The memory may bea read-only memory, random access memory, volatile memory, non-volatilememory, static memory, dynamic memory, flash memory, cache memory,and/or any non-transitory memory device that stores digital information.

As may be used herein, the term “operable to” or “configurable to”indicates that an element includes one or more of circuits,instructions, modules, data, input(s), output(s), etc., to perform oneor more of the described or necessary corresponding functions and mayfurther include inferred coupling to one or more other items to performthe described or necessary corresponding functions. As may also be usedherein, the term(s) “coupled”, “coupled to”, “connected to” and/or“connecting” or “interconnecting” includes direct connection or linkbetween nodes/devices and/or indirect connection between nodes/devicesvia an intervening item (e.g., an item includes, but is not limited to,a component, an element, a circuit, a module, a node, device, networkelement, etc.). As may further be used herein, inferred connections(i.e., where one element is connected to another element by inference)includes direct and indirect connection between two items in the samemanner as “connected to”.

As may be used herein, the terms “substantially” and “approximately”provides an industry-accepted tolerance for its corresponding termand/or relativity between items. Such an industry-accepted toleranceranges from less than one percent to fifty percent and corresponds to,but is not limited to, frequencies, wavelengths, component values,integrated circuit process variations, temperature variations, rise andfall times, and/or thermal noise. Such relativity between items rangesfrom a difference of a few percent to magnitude differences.

Note that the aspects of the present disclosure may be described hereinas a process that is depicted as a schematic, a flowchart, a flowdiagram, a structure diagram, or a block diagram. Although a flowchartmay describe the operations as a sequential process, many of theoperations can be performed in parallel or concurrently. In addition,the order of the operations may be re-arranged. A process is terminatedwhen its operations are completed. A process may correspond to a method,a function, a procedure, a subroutine, a subprogram, etc. When a processcorresponds to a function, its termination corresponds to a return ofthe function to the calling function or the main function.

The various features of the disclosure described herein can beimplemented in different systems and devices without departing from thedisclosure. It should be noted that the foregoing aspects of thedisclosure are merely examples and are not to be construed as limitingthe disclosure. The description of the aspects of the present disclosureis intended to be illustrative, and not to limit the scope of theclaims. As such, the present teachings can be readily applied to othertypes of apparatuses and many alternatives, modifications, andvariations will be apparent to those skilled in the art.

In the foregoing specification, certain representative aspects of theinvention have been described with reference to specific examples.Various modifications and changes may be made, however, withoutdeparting from the scope of the present invention as set forth in theclaims. The specification and figures are illustrative, rather thanrestrictive, and modifications are intended to be included within thescope of the present invention. Accordingly, the scope of the inventionshould be determined by the claims and their legal equivalents ratherthan by merely the examples described. For example, the componentsand/or elements recited in any apparatus claims may be assembled orotherwise operationally configured in a variety of permutations and areaccordingly not limited to the specific configuration recited in theclaims.

Furthermore, certain benefits, other advantages and solutions toproblems have been described above with regard to particularembodiments; however, any benefit, advantage, solution to a problem, orany element that may cause any particular benefit, advantage, orsolution to occur or to become more pronounced are not to be construedas critical, required, or essential features or components of any or allthe claims.

As used herein, the terms “comprise,” “comprises,” “comprising,”“having,” “including,” “includes” or any variation thereof, are intendedto reference a nonexclusive inclusion, such that a process, method,article, composition or apparatus that comprises a list of elements doesnot include only those elements recited, but may also include otherelements not expressly listed or inherent to such process, method,article, composition, or apparatus. Other combinations and/ormodifications of the above-described structures, arrangements,applications, proportions, elements, materials, or components used inthe practice of the present invention, in addition to those notspecifically recited, may be varied or otherwise particularly adapted tospecific environments, manufacturing specifications, design parameters,or other operating requirements without departing from the generalprinciples of the same.

Moreover, reference to an element in the singular is not intended tomean “one and only one” unless specifically so stated, but rather “oneor more.” Unless specifically stated otherwise, the term “some” refersto one or more. All structural and functional equivalents to theelements of the various aspects described throughout this disclosurethat are known or later come to be known to those of ordinary skill inthe art are expressly incorporated herein by reference and are intendedto be encompassed by the claims. Moreover, nothing disclosed herein isintended to be dedicated to the public regardless of whether suchdisclosure is explicitly recited in the claims. No claim element isintended to be construed under the provisions of 35 U.S.C. § 112(f) as a“means-plus-function” type element, unless the element is expresslyrecited using the phrase “means for” or, in the case of a method claim,the element is recited using the phrase “step for.”

What is claimed is:
 1. User equipment, comprising: a display; at leastone transceiver configured to communicate with an external biosensor,wherein the at least one transceiver receives biosensor data from thebiosensor; at least one processing circuit and at least one memorydevice, wherein the at least one memory device stores instructions whichwhen executed by the at least one processing device, causes the userequipment to: process the biosensor data to determine a level of nitricoxide (NO) in blood flow, wherein the biosensor data includes a firstPPG signal at a first wavelength and a second PPG signal at a secondwavelength; and generate a graphical user interface (GUI) that displaysthe biosensor data on the display of the user equipment.
 2. The userequipment of claim 1, wherein the user equipment is further configuredto: generate a GUI that displays one or more commands for controllingthe biosensor; receive user input indicating a command for thebiosensor; and transmit a command to the biosensor in response to theuser input.
 3. The user equipment of claim 1, wherein the firstwavelength of light has a high absorption coefficient for nitric oxide(NO) levels in blood flow and the second wavelength of light has a lowabsorption coefficient for NO levels in blood flow.
 4. The userequipment of claim 3, wherein the user equipment is further configuredto: obtain a value L_(λ1) using the first PPG signal; obtain a valueL_(λ2) using the second PPG signal; and determine a value R_(λ1, λ2)using a ratio including the value L_(λ1) and the value L_(λ2).
 5. Theuser equipment of claim 4, wherein the user equipment is furtherconfigured to: determine a level of nitric oxide (NO) in blood flowusing at least the value R_(λ1, λ2).
 6. The user equipment of claim 1,wherein the user equipment is further configured to: obtain a bloodglucose concentration level using at least the value R_(λ1, λ2) and acalibration.
 7. The user equipment of claim 1, wherein the userequipment is further configured to: determine a level of one or moreadditional substances in blood flow using the biosensor data.
 8. Theuser equipment of claim 1, wherein the user equipment is furtherconfigured to: determine a level of vasodilation using the biosensordata, wherein the level of vasodilation includes a measurement of alocalized change in width of a vessel from a localized relaxation ofvascular muscle cells within the vessel walls.
 9. The user equipment ofclaim 1, wherein the biosensor is implemented in a finger attachment andthe user equipment includes a smart phone.
 10. User equipment,comprising: a display; at least one transceiver configured tocommunicate over a cellular network and to an external biosensor; and atleast one processing circuit and at least one memory device, wherein theat least one memory device stores instructions which when executed bythe at least one processing device, causes the user equipment to: obtaina value L_(λ1) using an AC component of a first PPG signal; obtain avalue L_(λ2) using an AC component of a second PPG signal; obtain avalue R_(λ1, λ2) from a ratio including the value L_(λ1) and the valueL_(λ2); obtain a blood glucose level using the value R_(λ1, λ2); andgenerate a graphical user interface that includes the blood glucoselevel on the display.
 11. The user equipment of claim 13, wherein thefirst PPG signal is obtained at a first wavelength with the highabsorption coefficient for nitric oxide (NO) levels in blood flow andthe second PPG signal is obtained at a second wavelength with a lowabsorption coefficient for NO levels in blood flow.
 12. The userequipment of claim 10, wherein the user equipment is further configuredto: generate a command to a drug administrative device to administermedication.
 13. The user equipment of claim 10, wherein the userequipment is configured to: generate a message with the blood glucoselevel to a third party health care provider; and transmit the messageover a wide area network to the third party health care provider. 14.The user equipment of claim 10, wherein the user equipment is furtherconfigured to: determine a level of one or more additional substances inblood flow using the biosensor data.
 15. The user equipment of claim 10,wherein the user equipment is further configured to: determine a levelof vasodilation using the biosensor data, wherein the level ofvasodilation includes a measurement of a localized change in width of avessel from a localized relaxation of vascular muscle cells within thevessel walls.
 16. The user equipment of claim 10, wherein the biosensoris implemented in a finger attachment and the user equipment includes asmart phone.
 17. User equipment, comprising: one or more transceiversconfigured to communicate over a cellular network and to at least oneexternal biosensor; at least one processing circuit and at least onememory device, wherein the at least one memory device storesinstructions which when executed by the at least one processing device,causes the user equipment to: obtain a first AC component of a first PPGsignal around a first wavelength of light (λ1), wherein the firstwavelength of light is in a range of 370 nm to 410 nm; obtain a secondAC component of a second PPG signal around a second wavelength of light(λ1), wherein the second wavelength of light is in an infrared (IR)range; and obtain an R value from a ratio including the first ACcomponent and the second AC component.
 18. The user equipment of claim17, wherein the user equipment is further configured to: obtain an NOlevel using the value R_(λ1, λ2) and a calibration.
 19. The userequipment of claim 17, wherein the user equipment is further configuredto: obtain an blood glucose level using the value R_(λ1, λ2) and acalibration.
 20. The user equipment of claim 17, wherein the userequipment is further configured to: determine a level of vasodilationusing the biosensor data, wherein the level of vasodilation includes ameasurement of a localized change in width of a vessel from a localizedrelaxation of vascular muscle cells within the vessel walls.